[Cemented bipolar prosthesis in multimorbidity patients with coxarthrosis. Short- and intermediate-term results].

The treatment of coxarthrosis with the cemented Duopleet prosthesis represents an efficient alternative to total hip prosthesis in elderly and polymorbid patients. The early results show a tolerable rate of complications. The patients can be mobilized early. The mortality seems to be low. Medium-term results are satisfactory. The rate of protrusions is lower than in patients with common femoral head prosthesis. Paraarticular ossifications are seen frequently. In numerous patients we found pain with projection to the operated hip.


[Visualized three-dimensional reconstruction and image analysis in orthopedics and trauma surgery].

Computer tomography is a commonly used technique for detecting pathological alterations in soft tissue and the skeleton. The remote access to image informations as well as the allocation of display and processing tools via networks enables improved diagnostic and therapeutic practice in orthopaedic and traumatologic surgery. The realization of a user friendly image analysis system displays and processes the acquired images in a modality oriented manner. Our method is based on a unique file format and specific evaluation procedures to produce the input data for three-dimensional display and algorithms for the individual design of implants. Our image analysis system can process the data of conventional computer tomographies with three or more mm distance. In contrast to the available systems there is a low significance of radiation effects.


Role of ultrasound in medical management of patients with renal stone disease.

Eighty-three patients with radiographically opaque renal stones were evaluated prospectively with ultrasound and compared to KUB (kidneys, ureters, bladder) with tomograms (KUB/T) to further define the use of ultrasound in the evaluation of renal calculi. The presence or absence and the size, number, and location of stones were analyzed and correlated for each modality. Ultrasound detected the presence of renal stones in 77 of 83 (93%) patients. However, all of the stones were detected on ultrasound in only 60% of these patients. Thirty percent (80 of 269) of the papillary-calyceal stones seen on KUB/T were missed on US; 66% of the stones missed measured 2 mm or less. Although ultrasound can be used for detection of intrarenal stones, KUB/T is a more accurate imaging examination for determination of size and number of small stones.


Urolithiasis in a children's hospital: 1985-1990.

We performed a retrospective study of patients who had urinary tract stones and were seen at our hospital from 1985-1990. The study was intended to determine the prevalence of urolithiasis and optimal approaches to imaging. Clinical data and imaging studies of 87 patients were reviewed. The mean age was 15.7 years with a range of 3 months to 44 years. Fifty-four percent of patients were male. Most patients had a known predisposing cause for urolithiasis; patients with myelodysplasia and structural urologic problems predominated. Plain films were performed in 77 patients; 57% showed stones. Ultrasonograms were performed in 71 patients; 77% showed stones. Excretory urograms (EU) were performed in 49 patients; 84% showed either stones or their effect on the urinary tract. Computed tomographic (CT) scan was performed in 25 patients; all showed stones.


Adult onset of renal angiomyolipoma in a patient with tuberous sclerosis.

The growth of renal angiomyolipomas in adult tuberous sclerosis patients has not been previously reported. We report one such case of the growth of an angiomyolipoma in a previously documented angiographically normal appearing kidney after the contralateral kidney was removed for angiomyolipoma 15 years earlier.


Unusual renal oncocytomas: pathologic and CT correlations.

The unusual features of nine oncocytomas in five patients are reported herein. These include multiplicity in two, bilaterality in two, calcification in one, and association with renal cell carcinomas in three patients. Radiologists should be aware of these findings for this benign renal neoplasm.


Lymphangioma presenting as a small renal mass during childhood.

Renal lymphangioma is a very rare lesion. A case of lymphangioma that presented as a small, hyperechoic renal mass on sonography in a child is reported. On CT, the lesion appeared as a low-density, enhancing renal mass. Despite its rarity, lymphangioma should be considered in the differential diagnosis of such a lesion. A suspected lymphangioma may be evaluated by percutaneous biopsy.


Acute renal cortical necrosis: contrast-enhanced CT and pathologic correlation.

Acute renal cortical necrosis is a rare cause of acute renal failure that is usually associated with third trimester obstetrical complications. The appearance of this condition on contrast-enhanced computed tomography (CT) has rarely been described. A case of acute cortical renal necrosis is presented and the findings on contrast-enhanced CT are described. The pathologic correlation is also presented.


Renal peripelvic lymphatic cysts (lymphangiomas) associated with generalized lymphangiomatosis.

Renal peripelvic lymphatic cysts (lymphangiomas) are usually seen as an isolated finding. They appear as multiple mass lesions with low attenuation on computed tomography (CT), and show no contrast enhancement. We present a case of renal peripelvic lymphatic cysts associated with generalized lymphangiomatosis, and examined with magnetic resonance imaging (MRI), CT, and lymphangiography. Multiplanar MRI demonstrated the extent of disease, including retroperitoneal lesions. The lesions had low-signal intensity on T1-weighted and high-signal intensity on T2-weighted images. The diagnosis of generalized lymphangiomatosis was verified by renal sinus cyst puncture, lymphangiography, and tissue biopsy.


CT renal planimetry: effectiveness in the evaluation of individual renal function.

Computed tomographic (CT) renal planimetry was used to study individual renal function in 32 adult patients with urologic disease. CT results were well-correlated to reference methods (r = 0.88, P < 0.001), which were radionuclide studies (N = 9) or separate creatinine clearance (N = 23). The difference between planimetric data and reference methods did not exceed 14% in any case and was less than 10% in 26 cases.


Serial sonographic evaluation of "buckshot colic" following a penetrating gunshot wound.

This paper demonstrates the findings of various radiologic imaging modalities in a case of shotgun injury to the kidney. This case is unusual because buckshot entered the renal collecting system, and subsequently passed through the urinary tract in the urine, causing "bullet colic." References to such injury in the literature are discussed, along with role of each imaging modality in the initial and subsequent radiologic workup, with particular emphasis on the usefulness of ultrasonography in evaluation of this patient.


CT of the urinary tract after abdominoperineal resection for rectal carcinoma.

Computed tomography (CT) after abdominoperineal (AP) resection for rectal carcinoma is a routine procedure for the detection of recurrent tumor and distal metastases. We reviewed sequential CT scans after AP resection in 52 patients in order to see whether the urinary tract as a neighboring organ is involved in recurrent malignancy. Bladder displacement in itself was not associated with hydronephrosis. Such hydronephrosis developed, however, in 14 patients--13 with a presacral mass, and one with retroperitoneal lymphadenopathy. In 23 of the 52 patients a presacral mass appeared, either fibrosis, infection, or recurrence. Severe hydronephrosis was found only with malignancy. We suggest that marked hydronephrosis associated with a presacral mass after AP resection is an indirect sign of malignancy.


Non-Hodgkin lymphoma of the ureter: CT demonstration with pathologic correlation.

A case of a 42-year-old man with non-Hodgkin lymphoma of the ureter is reported. Diffuse lymphomatous infiltration of the ureter occurs rarely and is an uncommon cause of ureteral obstruction. Imaging-pathologic correlation is presented with CT images and autopsy specimens.


Salpingoureteral fistula: CT appearance.

Laparoscopic laser surgery is becoming increasingly common as treatment for endometriosis. We report a case of computed tomographic (CT) demonstration of salpingoureteral fistula secondary to laparoscopic laser surgery.


Congenital bladder diverticulum: an unusual presentation with abdominal mass, urinary retention, and renal failure in a young adult.

Computed tomographic (CT) evaluation of an abdominal mass diagnosed a huge 2-L congenital bladder diverticulum that caused urinary retention and ureteral compression leading to renal failure. The patient's renal failure resolved with decompression. His voiding dysfunction and retention resolved following diverticulectomy.


Urinary bladder leiomyoma: magnetic resonance imaging findings.

Benign urinary bladder tumors are very rare, leiomyoma being the most common among them. We wish to report a case and discuss the radiological findings with special emphasis on magnetic resonance (MR) imaging.


Fibrotic lesions of the testicle: sonographic patterns mimicking malignancy.

All testicular sonograms performed over a 2.5-year period were retrospectively reviewed, yielding eight patients with pathologically proven lesions consisting primarily of tubular sclerosis and interstitial fibrosis. Only two patients (25%) had a palpable abnormality. A variety of sonographic patterns was found, including focal hypoechoic or hyperechoic lesions and diffuse heterogeneity of the testicular parenchyma. The clinical and sonographic findings prompted open biopsy or orchiectomy in all cases. In the same time period, nine pathologically proven testicular malignancies were evaluated sonographically and displayed either well-defined hypoechoic or diffusely heterogeneous echo patterns. All but two of these patients (78%) had palpable abnormalities. This study demonstrates a significant overlap in the sonographic appearance of benign fibrotic lesions and testicular malignancies. When careful palpation of a sonographically heterogeneous or focal hypoechoic lesion fails to reveal a mass and serum tumor markers are negative, an open biopsy with frozen section analysis should be considered rather than proceeding directly to orchiectomy. Homogeneously hyperechoic masses can be considered benign and do not require surgery.


CT of uterine cervical myeloma: case report.

Myelomatous involvement of the uterine cervix is rare and, to our knowledge, has not been reported previously in the radiologic literature. This report describes the computed tomographic (CT) findings and reviews differential diagnostic considerations.


Metastatic transitional cell carcinoma simulating primary ovarian malignancy.

A case of metastatic transitional cell carcinoma (TCC) to the ovaries in a patient with prior grade I TCC of the bladder, which morphologically resembled a primary ovarian malignancy on computed tomography (CT), is described. Other tumors whose ovarian metastases can resemble primary ovarian tumors are also listed.


Current usage of nonionic contrast.

All physicians who had billed Pennsylvania Blue Shield for at least three intravenous contrast studies during 1989 were surveyed on their use of nonionic versus ionic contrast. This surveyed group represents a diversity of hospital sizes, practice types, and group sizes. Of the 383 physician groups surveyed, responses were obtained from 285. The majority of the responding groups were radiologists (94.0%). Nonionic contrast is utilized in 41.3% of all intravenous studies. Radiologists use nonionic contrast in a much greater proportion than nonradiologists (P < 0.0001), with 17.6% of radiologists utilizing nonionic contrast in all of their patients. Conversely, 75% of nonradiologists utilize ionic contrast in all of their patients. For all physician groups surveyed, 40.3% utilize nonionic for at least 50%, while 27.6% use nonionics for more than 75% of their patients. The routine use of steroid premedication prior to the injection of ionic contrast is not a common practice. The increased utilization of nonionic contrast found in this survey may reflect the cross-section of physicians and practice types surveyed or may represent changing practice patterns among physicians utilizing contrast material.


Update on interventional treatment of urinary obstruction.

During the last 20 years percutaneous nephrostomy has evolved as one of the basic procedures in the management of obstructive uropathy. This procedure is now widely available, it is relatively safe, and it offers rapid treatment of urinary obstruction regardless of underlying cause. Percutaneous nephrostomy is also the first step in a variety of antegrade ureteral procedures, including stent placement and ureteral dilation.


[The immunoenzyme detection of the HIV-1 antigen by using monoclonal antibodies to protein p24].

A test system using monoclonal antibodies to HIV p24 was developed for solid-phase ELISA for detection of HIV antigen (AG) which helped detect the content of AG in samples with trace concentrations, less than 25 pg/ml. The test system can be used for AG monitoring in natural specimens (serum of HIV-infected patients and culture medium of infected cells) and for determination of antigen-recombinant product of HIV gag gene.


[The anti-HIV activity of beta-glycyrrhizic acid].

The anti-HIV activity of beta-glycyrrhizic acid (GA) and various derivatives was studied using various strains of HIV-1 and HIV-2 in primary infected lymphoblastoid cells MT-4 and monocyte cell line U-973 chronically infected with HIV-1 and containing provirus (GKV 4005). Beta-glycyrrhizic acid and its derivatives were shown to effectively inhibit HIV-1 reproduction in MT-4 cells. The antiviral effect of beta-GA sodium salt exceeded that of AZT in cells GKV 4005. The selective indices for some GA salts were evaluated, namely: 53 for 1NH4 salt of GA, 6.7 for 1K-2Li salt of GA; 4.45 for GA. The mechanism of GA action is discussed.


[The determination of the genotype of natural reassortant influenza A viruses according to the core protein genes by the methods of competitive dot hybridization and sequencing].

Simultaneous circulation of different subtypes of influenza A viruses provides conditions for reassortant strains formation. A comparative investigation of genome of 47 influenza A virus strains (H1N1, H2N2, and H3N2) was carried out by competitive dot hybridization technique and sequence analysis of some of cDNA-copies of the virus genes. All the genes of 43 strains encoding nonglycolysed proteins corresponded to the serum subtype of surface glycoproteins. The reassortant pattern of genome for some genes of core proteins was revealed in 4 viruses. All the dot hybridization data were completely confirmed by sequence analysis of the genes.


[The specific reactivity of cDNA and deoxyoligonucleotide probes, complementary to the tick-borne encephalitis virus genome, with the RNA of strains of different geographical origins].

Hybridization experiments with RNA of 143 tick-borne encephalitis (TBE) virus strains isolated in different parts of the distribution area were used to study the reactivity of kDNA- and a set of 10 synthetic deoxyoligonucleotide probes. The kDNA probe under certain conditions was shown to hybridize with RNA of all the strains under study, and under other (strict) hybridization conditions did so selectively with a small number of strains. The capacity of oligonucleotide probes for hybridization with RNA of TBE virus strains varied from 12% to 100%. The differences in the hybridization activity of kDNA- and oligonucleotide probes complementary to the genomes of the Sophyin strain (Far-Eastern subtype) and Neudorffle strain (Western subtype) with TBE virus strains were used for differentiation of the strains into six genetic variants. Comparison of the reactivity of molecular probes in experiments with RNA of TBE virus strains and viruses of the TBE complex showed that the differences of the strains belonging to different genetic variants from the prototype Sophyin strain were comparable to those of some members of the TBE complex, with the exception of Powassan virus. These data attest to the necessity of further studies dealing with specification of the taxonomy of TBE complex viruses.


[The geographical distribution of genetic variants of the tick-borne encephalitis virus].

Geographic distribution of 185 tick-borne encephalitis (TBE) virus strains isolated in 8 physico-geographic areas and classified into six genetic variants was analysed. The strains of genetic variant I homologous to the Sophyin prototype strain were found to occur predominantly in the Far East and also frequently found in Western and North-Western parts of the East European plain. The vast territories from lake Baikal in the East to Ukraine in the West harbor mostly the strains significantly different from the Far-Eastern Sophyin strain. Hybridization experiments with oligonucleotide probes specific for the Neudorffle strain showed that the strains genetically similar to the virus of central European encephalitis occurred also in Eastern Europe and Western Siberia. It is concluded that a relationship exists between genetic types of TBE virus and their geographic origin.


[The effectiveness of lanthanide immunofluorescence and immunoenzyme analyses in differentiating viruses of the tick-borne encephalitis complex].

Comparison of the efficacy of time-resolved fluoroimmunoassay (TR-FIA) and two variants of enzyme immunoassay: conventional (EIA-1) and one using biotin-streptavidin system (EIA-2), in differentiation of viruses of the tick-borne encephalitis complex showed that, their specificity being similar, the TR-FIA method was 2-4 times as sensitive as EIA-2 and 8-32 times as sensitive as EIA-1. When the reactivity of the antigens was assessed by titers, the differentiating capacity was found to be similar and to depend upon the specificity of "sandwich"-forming antibodies and the sensitivity of the immunoassay. When the reactivity of the antigens was assessed by relative reactivity in 4 test systems of different compositions, the differentiating capacity of TR-FIA was higher than that of EIA-1 and EIA-2 which allowed additional differentiation of 2 groups of viruses on the basis of qualitative characteristics of reactivity.


[A lyssavirus with an unusual antigenic structure isolated from a bat in southern Kyrgyzstan].

Examination of 191 specimens of Chiroptera in Osh Province of Kyrgyzstan yielded 1 strain of lyssavirus from Myotis blythi, the isolate not belonging to serotype 1. The virus was designated Aravan by the area of its isolation. Its antigenic structure was studied using antinucleocapsid monoclonal antibodies of the Wistar Institute (Philadelphia, ISA) and Central Veterinary Laboratory of Great Britain (Waybridge, Great Britain). The paper presents its antigenic profile, brief characteristics of similarity and differences of the Aravan strain and known lyssavirus serotypes.


[The determination of measles antibody titers in the latex agglutination reaction].

A new latex agglutination test (LAT) for detection of antibodies to measles virus in blood sera was developed. The latex diagnosticum consists of polymeric microspheres of national make carrying on their surface covalently bound measles virus antigen. The data on the specificity and sensitivity of the test are presented, and the results of titrations of blood sera from schoolchildren by traditional HI test and LAT are compared. LAT was shown to be highly sensitive, much simpler than the available methods for detection of measles antibodies and more economic, and therefore may be recommended for mass surveys.


[The isolation of measles virus strains and the study of their hemagglutinating activity].

Three measles strains Gag, Il, and Buk, were isolated from a suspension of mononuclear cells derived from measles patients in the active stage of the disease. Continuous Vero cell cultures were used for virus isolation. In the infected cell culture, all the isolates produced symplasts of different sizes and star-shaped or spindle-shaped multinuclear cells. The specificity of the cytopathic effect was proved by the adsorption of monkey erythrocytes on the surface of virus-affected cells. The isolates were identified in neutralization and HI tests with different immune preparations: measles gamma-globulin (national standard), hyperimmune rabbit sera to measles (Edmonston strain), rubella, and mumps viruses, S. sonnei and S. flexneri, as well as with sera from measles patients and subjects vaccinated with live measles vaccine L-16. The results of identification attest to isolation of 3 measles virus strains, one of which (Buk) possesses particularly high hemagglutinating activity.


Chlamydial infections in selected populations in Jamaica.

The importance of Chlamydia trachomatis as a cause of genital tract infection in Caribbean countries is largely unknown. Two hundred and sixteen cervical and urethral specimens were collected from patients with cervicitis and urethritis attending a Sexually Transmitted Diseases (STD) Clinic, a Gynaecology Clinic and a Family Planning Clinic in Kingston. Specimens were tested for chlamydiae by direct immunofluorescence and cell culture methods. They were also investigated for N. gonorrhoeae infections. Seventy-two of 138 patients (52.2%) at the STD Clinic were positive for chlamydiae; 28 of 50 (56.0%) from the Gynaecology Clinic and 11 of 28 (39.3%) from the Family Planning Clinic were positive. The prevalence of C. trachomatis (52.3%) was higher than that of N. gonorrhoeae (11.1%) in all groups. The results indicate that C. trachomatis is a common cause of genital tract infections in Jamaica.


Hepatic ultrastructure in children with protein-energy malnutrition.

Samples of liver from eight children who died from malnutrition with its complications were studied by electron microscopy. Specimens were taken within one hour of death. These tissues had changes consistent with severe terminal illness, including mitochondrial swelling, with loss of matrix granules, disorganization of cristae, and evidence of calcium influx. Glycogen tended to be scanty. Lipid droplets were frequent. Endoplasmic membranes were depleted, and focal cytoplasmic degradation was frequent. Intracanalicular cholestasis was striking in four cases with loss of microvilli. Peroxisomes were depleted. This may be significant as peroxisomes are pivotal in the processing of very long-chain fatty acids, in cholic acid metabolism and in elimination of free radicals. The observations were compared with previous reports in the literature, and with seven biopsies taken in 1970 from malnourished children who recovered. One, obtained on the fourth day, from a child with marasmus, showed atrophy of cellular organelles. The other samples were biopsied during the recovery phase, and displayed considerable restoration to normal morphology. Mitochondria had prominent matrix granules. Peroxisomes were frequently seen. There was no evidence of cholestasis.


Unstable diabetic state produced by a small dose of streptozotocin in rats.

A diabetic state was induced with a single intraperitoneal dose (45 mg/kg) of streptozotocin in rats. Their fasting blood glucose concentrations oscillated between 12.7 +/- 1.9 mmol/l and 4.6 +/- 0.6 mmol/l during 35 days of monitoring. Their body weights were also reduced, while controls gained weight, although food consumption was not significantly different. Also, within the first 1/2-hour of the oral glucose tolerance test, blood glucose concentration increased in the diabetic and the control rats, but only in the control rats was there a simultaneous increase in serum IRI concentration (7.2 +/- 8 x 10(2) pmol/l to 27.0 +/- 5.2 x 10(2) pmol/l) which, like the blood glucose concentration, subsequently fell to fasting level in the control rats. In the diabetic rats, however, it was not until the following hour of the tolerance test that serum IRI concentration increased (3.4 +/- 0.3 x 10(2) pmol/l to 65.0 +/- 12.5 x 10(2) pmol/l) and blood glucose concentration began to fall. By the end of the test in the diabetic rats, blood glucose concentration fell but remained significantly higher than the control value. Additionally, no pancreatic tumours were identified in these diabetic rats. The results therefore suggest that an unstable diabetic state was produced by streptozotocin because the threshold for insulin secretion by glucose was increased, while the production of insulin by the pancreas was not significantly affected.


[The functional role of the glycosylation of viral components].

An inhibitory analysis of the role of glycosylation and glycoproteins in the manifestations of the most important properties of African swine virus was carried out using a set of strains and variants with contrasting characteristics. Glycoproteins were shown to realize some virus functions such as virulence and its variability, intracellular transport and exocytosis of virions, hemadsorption, but not immunological recognition of the infected cells by cytotoxic T-lymphocytes.


Computed tomography of the calves. A screening procedure in the diagnosis of unilateral thrombosis of the deep veins of the lower limbs.

A prospective study of twelve patients, referred to the Department of Radiology of the University Hospital of the West Indies between March, 1990 and November, 1991 with a clinical diagnosis of deep vein thrombosis, was undertaken. All patients had computed tomography of the calves, as well as venography of the affected limb. Six patients (50%) had positive venograms. Of these, five had a difference of greater than 10% between the areas of the muscular compartments of the two limbs. Six patients had negative venograms but only three demonstrated a difference of a similar magnitude. The ratios of the area of the muscular compartment to the total limb area were also compared. Two of the six patients with positive venograms showed a greater ratio in the affected limb. One of the six patients with negative venograms showed a greater ratio in the affected limb. In this study, 83.3% of patients who did not have thrombosis of the deep veins of the calves had a ratio of muscular area to total limb area that was less than or equal to that of the unaffected side. This latter finding provides a potentially useful means of screening patients referred for venograms.


Solitary rectal ulcer syndrome.

Solitary Rectal Ulcer Syndrome (Rectal Prolapse Syndrome) is an uncommon and imperfectly understood entity which, however, should be included in the differential diagnosis of ano-rectal symptoms. This article reports on the nine cases so far diagnosed at the University Hospital of the West Indies (UHWI), and offers a brief review of the condition.


Arthroscopic surgery of the knee.

Seventy-nine arthroscopies of the knee were performed between January 1989 and March 1992. There were sixty-one males and eighteen females. The age range was from 12 to 78 years and the mean age was thirty-four years. Fifty patients had torn menisci. The menisci were removed arthroscopically in forty cases, arthrotomy being needed in the other ten cases. Following arthroscopic meniscectomies, patients returned to work in seven days, and to sporting activities in eight to ten weeks. Chondromalacia of the patella and femoral condyles were diagnosed in nineteen cases. These were treated by arthroscopic shaving and drilling of the irregular articular surfaces. In two cases, the procedure was used for assessment prior to other operations. Arthroscopy failed in two other patients due to pain and swelling and was normal in the remaining six cases.


Shoulder dystocia: an obstetrical nightmare.

A nine-year review of 103 cases of shoulder dystocia identified obesity, diabetes mellitus and post-datism as important predisposing risk factors. There was a positive correlation with birthweight. Abnormal labour patterns were invariably absent and perinatal outcome was disastrous. The best strategy is to anticipate and avoid this obstetrical emergency.


Diagnostic hysteroscopy.

Diagnostic hysteroscopy was performed on 100 patients. The most frequent indication was abnormal uterine bleeding. In premenopausal women, submucous fibroids were the main findings and in post-menopausal women, 59 per cent had an atrophic endometrium. Precise localization of the missing intrauterine contraceptive devices was achieved in all cases. Hysteroscopy improved diagnostic accuracy and reduced the need for blind curettage.


Shared-induced paranoid disorder folie à deux between mother and son.

A case of shared-induced paranoid (psychotic) disorder (DSM III-R, 1987) between mother and son is presented. This disorder may be a more frequently occurring disorder than is generally recognised. It is suggested that more detailed family and social investigations be undertaken to unearth psychopathology in the social environment of the patient. In cases involving relatives, this may be another dimension to the genetic influence on mental illness. This is the first case reported in the West Indian medical literature.


Retroperitoneal lipoblastoma. Report of a case and review of the literature.

We present the first case of retroperitoneal lipoblastoma at the University Hospital of the West Indies. This is one of the few reported cases in the general literature.


Eosinophilic granuloma of the cervical and thoracic spine in a child.

A case of eosinophilic granuloma affecting a cervical vertebra, thoracic vertebra and pelvis in a child is reported. We present this case because multifocal eosinophilic granuloma lesions of the spine are rare and can present as this case did with both diagnostic and therapeutic problems. Preoperative diagnosis may be made by X-ray, isotope bone scan and needle biopsy, avoiding unnecessary surgical intervention.


Very low calorie diets and pre-fasting prolonged QT interval. A hidden potential danger.

The association of torsade de pointes and a prolonged electrocardiographic QT interval is well described. A prolonged QT interval may be congenital or acquired in several ways--by the use of anti-arrhythmic agents exemplified by quinidine, by the presence of hypocalcaemia or hypokalaemia, by the use of psychotropic drugs, and by the presence of intrinsic cardiac disease or bradycardias. Possibly less well appreciated is the potential for drastic weight loss to prolong the QT interval, as the present case report illustrates. A young woman weighing 244 pounds lost 24 pounds in two weeks with a consequent prolongation of QTc interval from pre-diet value of 0.57 seconds to 0.72 seconds at admission, when severely symptomatic paroxysms of torsade de pointes were recorded. Successful therapy with lignocaine and prompt re-feeding suppressed the arrhythmia and, three days later, the QTc was reduced to almost its pre-diet state. A (UK) DHSS report offers guidelines in the use of very low calorie diets. This case suggests that a pre-diet electrocardiogram should be carefully assessed for QT prolongation before initiation of dieting to achieve serious weight loss.


[Circulating immune complexes and complement fragment iC3b in chronic polyarthritis during 12 months therapy with oral enzymes in comparison with oral gold].

In the course of a double-blind randomized study lasting 1 year 19 patients suffering from ensured rheumatoid arthritis (ARA criteria) were treated with oral hydrolytic enzymes or oral gold salts. The effects of these therapies were examined in regard to changes in serum concentrations of circulating immune complexes (CIC) and the complement component iC3b. After 12 months treatment with oral enzymes we determined a therapeutically wanted significant decrease of CIC whereas CIC increased up to 6 months. The best but not significant result under therapy with oral gold salts concerning CIC was a decrease in 6 out of 9 patients after 9 months. The complement component iC3b diminished with either therapy during the first 6 months and increased afterwards. As well as the reduction of circulating immune complexes, the intensified inactivation of C3b into iC3b during the second half-year with both treatments indicates that there might be a slight improvement of the pathologically changed immunoreactions after 6 months only. Concerning the examined laboratory parameters, no significant difference was found between both therapies.


[Comparison of results of daily blood pressure self-monitoring and general practice monitoring within the scope of a study assessing treatment of hypertension with quinapril].

24 hour blood pressure monitoring is a well established method in the field of antihypertensive research. Patients self recorded blood pressure values are an additional option to overcome the disadvantages of casual office readings--however they are not frequently used within intervention trials. To prove the usefulness of selfrecordings in clinical trials we investigated both selfrecordings taken twice a day and casual readings within intervals of 1 to 3 weeks, in this study on the efficacy and tolerability of the ACE-inhibitor Accupro. 108 hypertensive patients (grade WHO I to II) were included in this trial for ten weeks. Although blood pressures were measured by the patients using sphygmomanometers of the same type and the physicians, decisions to treat or to increase dosage were based on the patients' recordings only. Accupro was dispensed according to the package leaflet at a daily dosage of 5 mg up to 40 mg. In case of failing response to monotherapy, Accupro was combined with Diltiazem or with a diuretic. 7 patients discontinued the treatment due to mild adverse events, one did not cooperate. 82 of the remaining patients were treated effectively with Accupro monotherapy--60 (73%) got one dose daily, 22 (27%) 2 doses per day,--and in 18 patients a drug combination was required. Therapeutic response (RRd < or = 90 mm Hg) was gained within 86 of the 100 evaluable patients according to the doctors' and 83 according to the patients' records. In this respect the two methods used gave comparable overall results. This somewhat surprising fact is due to the design of the study, because treatment decisions were based on the selfrecordings only. Clinical trials based on selfrecordings are in some points preferable to casual office readings: As patients being normotensive at home should not be included into an interventional study, a change of dosage within this group is avoided. Additionally the compliance of a cooperative patient taking his blood pressure twice daily is at a high level. Measurements of each single patient may be evaluated statistically by time series-analysis regarding longterm distribution of blood pressure-values. Taking the means of selfrecordings over adequate time-intervals eliminates the influence of "outliers" (occasionally extremely high or low values) and also reduces the standard deviation compared to that of the casual readings. Research work based on self recordings provides more information and therefore more security for treatment decisions.


[Medically correct sitting, does it exist?].

In the relaxed sitting position on conventional seats the lordosis of the lumbar spine is often lost. This can cause overstress of the discs, ligaments and muscles. Ergonomically correct seating aims at avoiding this. Some of the relevant seat characteristics concern back rest, seat base, arm rests, upholstering, individual adaptation and integration into the environment. In addition to office seats, "alternative" seats, car seats, and school benches are discussed. Since sitting invariably is associated with unfavourable statics, "correct" seating is a contradiction in itself. The aim can only be to minimize injury and to define a seat which causes the least damage. Considering its potential importance, the further neglect of this subject by medical research is unjustified.


Burn depth: a review.

Despite the plethora of technologic advances, the most common technique for diagnosing burn depth remains the clinical assessment of an experienced burn surgeon. It is clear that this assessment is accurate for very deep and very shallow burns. But since clinical judgment is not precise in telling whether a dermal burn will heal in 3 weeks, efforts to develop a burn depth indicator are certainly warranted to accurately determine which dermal burns to excise and graft. This review summarizes the considerable literature in which a variety of techniques to determine burn depth have been used.


Pre-operative radiotherapy as adjuvant treatment in rectal cancer.

From January, 1975 to December, 1987, 241 patients with rectal cancer underwent pre-operative irradiation and surgical resection. The radiation was delivered with 25 MeV photons, 5 days per week by 2.4 grays fractions up to a total dose of 36 grays. Surgery was curative in 195 patients; 57% had abdomino-perineal resection. Irradiation had to be discontinued in 3 patients and 4 patients subsequently developed severe acute ileitis. Postoperative mortality rate was 2.9%. The most frequent postoperative complications were delayed healing of abdominal wounds (18%) and perineal wounds (14%). Severe late complications occurred in 27 (13%) patients. The incidence of intestinal obstruction was 5%. Follow-up survivors ranged from 18 months to 13 years. Local failure occurred in 24 (12%) of the 195 patients. Local failure rates were 10% for Dukes' A tumors, 11.6% for Dukes' B, and 22.7% for Dukes' C tumors. Five and 10 year actuarial survival rates after curative surgery were 70% and 52%. The Dukes' classification was the only factor that influenced survival.


Evaluation of the laparoscopic cholecystectomy on patients with simple and complicated cholecystolithiasis.

Laparoscopic cholecystectomy is now a well described method for the treatment of cholelithiasis. The purpose of this paper is to define its implementation, limits, risks and indications. Following a prospective method, the results of this treatment were compared in 187 patients with simple cholelithiasis and 75 patients with complicated cholelithiasis. Cholecystectomy was performed with a straight optic introduced through the paraumbilical region, and coupled with video camera. Two, 3, or 4 other trocars were inserted and placed as required by anatomic conditions. In the group with simple cholelithiasis, laparoscopic cholecystectomy was performed in 99% of the patients while in the group with complicated cholelithiasis the procedure was achieved in 75% of the patients. Immediate laparotomy was done in 1% and 25% of cases respectively in both groups. No interventional mortality occurred. Postoperative complications have been acceptable (1.6% and 2.7%), with no late complications reported. Our study shows that laparoscopic cholecystectomy is feasible in the majority of cases of complicated cholelithiasis and that the main advantages of this method were retained.


"Endemic" idiopathic portal hypertension: report on 32 patients with non-cirrhotic portal fibrosis.

The clinical features, surgical management, and long term follow up of 32 patients from Iran with idiopathic portal hypertension are reported. Many features of the disease are similar to those reported from India and Japan. The unsuspected finding was a 46% history of marked pica of clay (geophagia) in a subset of 26 patients. In addition, 81% of our patients had a prolonged prothrombin time, despite otherwise normal to minimally abnormal liver function tests. Liver biopsies revealed intrahepatic periportal fibrosis with subintimal thickening of terminal branches, and in many specimens a striking peri-ductular fibrosis was seen in the adjacent bile ducts. The spleen was very large with a dilated artery (external diameter: 11 mm to 15 mm). Portal venous pressure (PVP) was measured intra-operatively before and after clamping the splenic artery (SA). Clamping the SA consistently caused a decreased in PVP which ranged from 2.0 to 18.2 cm water with the mean +/- SEM of 9.7 +/- 1.5 cm water (p < 0.001, paired t-test). It was equivalent to 32.3 +/- 3.6% decrease in PVP. Fifteen selected patients (Group I) were managed with splenectomy with excellent short and long term results. The selection criteria for splenectomy included a decrease in PVP to < 24 cm of water after clamping the SA. Three patients from this group were re-examined 10 to 12 years following splenectomy. Cirrhosis had not developed, but the minimal abnormalities in the liver function tests had persisted.(ABSTRACT TRUNCATED AT 250 WORDS)


The surgical management of benign and malignant thyroid neoplasms in Marshall Islanders exposed to hydrogen bomb fallout.

On March 1, 1954, a serious fallout accident occurred during the United States atomic testing program at Bikini in the Trust Territory of the Pacific Islands. Following the detonation of a large thermonuclear device (known as Bravo) an unexpected shift in winds resulted in deposition of radioactive debris on several inhabited atolls in the Marshall Islands. During the early post-detonation period military, sea, and air surveys traced the hottest portion of the parabolic cloud as it drifted in an ever widening pattern of diminishing concentration eastward and southeast of Bikini. The center of the cloud passed North of the Rongelap Atoll, which was the nearest inhabited atoll. This report concerns the development of thyroid lesions, the special circumstances encountered during thyroid surgery, and the results of the surgical management of benign and malignant lesions that were subsequently encountered in this population.


Percutaneous drainage of pancreatic pseudocysts: a prospective study.

We classify pancreatic pseudocysts in 3 types: post-necrotic type I, related to acute pancreatitis; post-necrotic type II, related to an acute attack superimposed on chronic pancreatitis; and retention type III, due to chronic pancreatitis with ductal stricture. A prospective study on percutaneous catheter drainage of post-necrotic pseudocysts (type I and II) was undertaken from 1987 to 1990. Twenty-three pseudocysts in 21 patients were drained. Overall recurrence rate was 4%; 2 patients had fistulization of the catheter into bowel; no deaths occurred. The procedure was successful in all type I cysts; in type II cysts it was associated with prolonged drainage and increased risk of complications when cyst-duct communication was present. Percutaneous drainage has no role to play in type III retention cysts. Guidelines regarding indications for treatment and the techniques employed are described.


Burn shock resuscitation.

The goal of fluid resuscitation in the burn patient is maintenance of vital organ function at the least immediate or delayed physiological cost. To optimize fluid resuscitation in severely burned patients, the amount of fluid should be just enough to maintain vital organ function without producing iatrogenic pathological changes. The composition of the resuscitation fluid in the first 24 hours postburn probably makes very little difference; however, it should be individualized to the particular patient. The utilization of the advantages of hypertonic, crystalloid, and colloid solutions at various times postburn will minimize the amount of edema formation. The rate of administration of resuscitation fluids should be that necessary to maintain satisfactory organ function, with maintenance of hourly urine outputs of 30 cc to 50 cc in adults and 1-2 cc/kg/% burn in children. When a child reaches 30 kg to 50 kg in weight, the urine output should be maintained at the adult level. With our current knowledge of the massive fluid shifts and vascular changes that occur, mortality related to burn-induced hypovolemia has decreased considerably. The failure rate for adequate initial volume restoration is less than 5% even for patients with burns of more than 85% of the total body surface area. These improved statistics, however, are derived from experience in burn centers, where there is substantial knowledge of the pathophysiology of burn injury. Inadequate volume replacement in major burns is, unfortunately, common when clinicians lack sufficient knowledge in this area.


Pathogenesis of edema formation in burn injuries.

One of the obvious acute features of cutaneous thermal injury is the swelling of the involved tissue. This swelling is caused by a fluid shift from circulating plasma. Along with the evolution of intravenous fluid therapy in trauma and surgery, the implementation of such therapy to burn victims has improved survival. Edema generation aggravated by fluid therapy may, however, represent a source of increased morbidity. This paper presents a review of the literature on postburn edema generation, focusing mainly on fluid physiology. It is well documented that fluid is lost from the circulation into burned tissue because of a moderate increase in capillary permeability to fluid and macromolecules and a modest increase in hydrostatic pressure inside the perfusing microvessels. Recently it was discovered that a very negative interstitial pressure develops in thermally injured skin. This pressure constitutes a strong "suction" adding markedly to the edema generating effect of increased capillary permeability and pressure.


Smoke inhalation: diagnosis and treatment.

Smoke inhalation, defined as airway or pulmonary parenchymal injury resulting from the inhalation of toxic combustion products, presents with a wide range of severity in patients with and without skin burns. In patients with severe injuries, the diagnosis is obvious on the basis of the history and clinical presentation; in patients with less severe injuries or those in whom the clinical consequences are delayed, diagnostic precision is difficult because diagnostic clues provide only indirect information. There is no specific treatment so diagnosis is not critical for patient management. Patients at risk include 20% to 30% of flame burn victims who should receive vigorous supportive care. The mortality rate of smoke inhalation victims without a burn is < 10%. With a burn the mortality rate is 30% to 50%, suggesting that thermal injury or its treatment is responsible for further lung damage. Endotracheal intubation provides definitive treatment for obstructed or soon-to-be obstructed patients. However the diagnosis of smoke inhalation per se is not an indication for airway intubation and respiratory support; 12% of patients without a burn require intubation versus 62% of those with a burn. A translaryngeal tube can be converted to a tracheotomy safely in burn victims; tracheotomies are easier to manage if burns of the neck are excised and grafted prior to placement. Mechanical ventilation with positive end expiratory pressure (PEEP) is the treatment for the pulmonary injury. The early lesions of smoke inhalation often progress in the context of sepsis and other complications of the burn illness to a clinical state consistent with adult respiratory distress syndrome.


The role of mediators in the response to thermal injury.

Inflammatory mediators play a major role in both the local burn wound and the systemic response to burn injury. Oxidant and arachidonic acid metabolites are involved in the initial burn edema process. The mediators as well as the cytokines released from activated macrophages also result in an early generalized inflammatory response. The later postburn hyper-metabolism is initiated and perpetuated by these same mediators, especially the cytokines, tumor necrosis factor, interleukin-1, and interleukin-2. Circulating endotoxin from the wound or the gut also appears to be involved. The postburn septic response is now recognized to be the result of inflammation; infection is not necessary. Mediator induced priming of the inflammatory cells by the burn itself results in an exaggerated response to infection in the postburn period. Defining the specific mechanism of injury and mediators involved can result in a major improvement in burn care, especially since many mediator inhibitors are already available for clinical use. It is essential that the clinician understand this pharmacologic manipulation in order to be able to optimally utilize these future advances.


Benefits and limitations of burn wound excision.

This review is intended to provide a balanced view of the role of surgical burn wound excision and closure within the larger context of the total care and rehabilitation of patients with burn injury. The historical background leading to present practice is outlined. The salient technical and logistical problems associated with the performance of wound excision are discussed, with emphasis on the necessity for expeditiously completing these procedures which are associated with major blood loss. A realistic analysis of the results of excisional therapy in patients with burns of varying severity is presented. Benefits attributable to the surgical phase of therapy become progressively more difficult to identify as the size of deep burns increases beyond 20% of total body surface area.


Biologic wound coverings in burn treatment.

A review of biologic wound coverings currently in use is presented. These include homografts, xenografts, embryonic membranes, and tissue derivatives. The indications, advantages, and disadvantages of such materials are discussed. Finally, future research directions are suggested.


Burn wound closure using permanent skin replacement materials.

Over the past decade, very significant advances in the development of clinically useful, permanent skin replacement materials have taken place. The most prominent and successful approaches to the physiological closure of an open wound have been either by creating a totally artificial dermal matrix material, by using culture techniques to expand cell populations for autologous transplantation, or by using a combination of these methods. As a result of substantial early progress in this field, permanent skin replacement materials as a treatment modality promise significant contributions to improved wound management and increased survival rates for patients with devastating soft tissue destruction such as massive burn injuries.


The immunologic response to thermal injury.

Thermal injury is associated with altered immune defense. Extensive and deep thermal injuries lead to depressed immune defense function with both cellular and humoral defense affected. There is an intricate interaction between various components of the immune system. The altered specific immune response is seen as a depressed ability to produce active rosette-forming cells. Depressed stimulation of lymphocyte proliferation as well as the mixed lymphocyte response have also been recorded following burns. These effects are modulated by the release of kinins, prostaglandins, anaphylatoxins, superoxides, and leukotrienes, all of which can influence the inflammatory response following thermal injury. The humoral immunity is altered as seen by decreased levels of immunoglobulins, activation of complement with release of anaphylatoxins, and formation of membrane attacking complexes leading to inflammation and cytolysis. The immune response to burns is also affected by factors other than this injury, such as nutrition or diseases such as diabetes mellitus or disorders of the lymphoproliferative type. The immune response is also influenced by some drugs used for other reasons such as steroids, chemotherapeutic agents, and topical agents used for burn wound care. The immune reaction to a burn is also influenced by the additive effect of superimposed infections. Removal of injured tissue without the need for extensive transfusion will improve the ability of the burned patients to use their immune defense system in a fruitful way.


The changing epidemiology of infection in burn patients.

Topical chemotherapy, prompt excision, and timely closure of the burn wound have significantly reduced the occurrence of invasive burn wound infection and its related mortality. Since wound protection is imperfect and invasive wound infection may still occur in patients with massive burns in whom wound closure is delayed, scheduled wound surveillance and biopsy monitoring are necessary to assess the microbial status of the burn wound and identify wound infections caused by resistant bacteria or non-bacterial opportunists at a stage when therapeutic intervention can control the process. As a reflection of the systemic immunosuppressive effects of burn injury, infection remains the most common cause of morbidity and mortality even though the occurrence of wound infections has been significantly decreased. Pneumonia is the most frequent infection occurring in burn patients today but the improvements in patient management, wound care, and infection control have made bronchopneumonia the most common form of this infection and gram-positive organisms the most common causative agents. The organisms causing bacteremia that exert a species specific effect on the mortality related to extent of burn injury and patient age have changed in concert with changes in wound flora. Infection control procedures, including scheduled surveillance cultures, utilization of cohort patient care methodology, strict enforcement of patient and staff hygiene, and patient monitoring have been effective in eliminating endemic resistant microbial strains, preventing the establishment of newly introduced resistant organisms, diagnosing infection in a timely fashion, instituting antibiotic and other necessary therapy in a prompt manner, and documenting the effectiveness of present day burn patient care and the improved survival of burn patients.


The metabolic effects of thermal injury.

Major thermal injury is associated with extreme hypermetabolism and catabolism as the principal metabolic manifestations encountered following successful resuscitation from the shock phase of the burn injury. Substrate and hormonal measurements, indirect calorimetry, and nitrogen balance are biochemical metabolic parameters which are useful and more readily available biochemical parameters worthy of serial assessment for the metabolic management of burn patients. However, the application of stable isotopes with gas chromatography/mass spectroscopy and more recently, new immunoassays for growth factors and cytokines has increased our understanding of the metabolic manifestations of severe trauma. The metabolic response to injury in burn patients is biphasic wherein the initial ebb phase is followed by a hypermetabolic and catabolic flow phase of injury. The increased oxygen consumption/metabolic rate is in part fuelled by evaporative heat loss from wounds of trauma victims, but likely also by a direct central effect of inflammation upon the hypothalamus. Although carbohydrates in the form of glucose appear to be an important fuel source following injury, a maximum of 5-6 mg/kg/min only is beneficial. Burn patients have accelerated gluconeogenesis, glucose oxidation, and plasma clearance of glucose. Additionally, considerable futile cycling of carbohydrate intermediates occurs which includes anaerobic lactate metabolism and Cori cycle activity arising from wound metabolism of glucose and other substrates. Similarly, accelerated lipolysis and futile fatty acid cycling occurs following burn injury. However, recent evidence suggests that lipids in the diet of burned and other injured patients serve not only as an energy source, but also as an important immunomodulator of prostaglandin metabolism and other immune responses. Amino acid metabolism in burn patients is characterized by increased oxidation, urea synthesis, and protein breakdown which is prolonged and difficult to reduce with current nutritional therapy. However, the current goal of nutritional support is to optimize protein synthesis. Specific unique requirements may exist for supplemental glutamine and arginine following burn injury but further research is needed before enhanced branched chain amino acids supplements can be recommended for burn patients. Recent research investigations have revealed the importance of enteral feeding to enhance mucosal defense against gut bacteria and endotoxin. Similarly, research has demonstrated that many of the metabolic perturbations of burns and sepsis may be due, at least in part, to inflammatory cytokines. Investigation of their pathogenesis and mechanism of action both at a tissue and a cellular level offer important prospects for improved understanding and therapeutic control of the metabolic disorders of burn patients.


Nutritional support of the burned patient.

Burn patients develop a number of physiologic alterations among which is a markedly increased metabolic rate. Other metabolic changes include an increased rate of glucose production and utilization, a decreased rate of lipid metabolism, and an increased rate of both protein catabolism and anabolism. These alterations can effect other physiologic parameters, including immune function. They necessitate administration of large quantities of calories and protein to achieve positive nitrogen balance. The physiologic derangements leading to the hypermetabolism and the methods for supplying the nutritional needs are discussed in this review.


Prevention and treatment of postburn scars and contracture.

The management of postburn reconstruction is complicated by the frequent occurrence of multiple reconstructive needs in a single patient. This article presents a simple, comprehensive approach to burn scar reconstruction. The primary aim of the surgeon is to prevent burn scar deformity by rapid wound closure, correction of tissue deficiencies, and assiduous attention to postoperative splinting and compression therapy. The initial step in managing secondary deformities is to prioritize reconstructive needs. Reconstruction is then carried out in a stepwise fashion aiming to restore active function first, followed by passive function, and finally addressing aesthetic reconstruction. Reconstructive techniques are applied in a hierarchy from simplest to most complex. Primary excision and closure of scars by reorientating the scar to the lines of relaxed skin tension can significantly improve appearance. The use of z-plasty, flap repair, and tissue expansion are also reviewed. Skin expansion, in particular, has become the standard management of postburn alopecia and, although associated with a relatively high rate of complication, has significantly improved the aesthetic appearance of such patients. The management of common problems affecting the face is discussed with particular reference to management of the eyelids, oral commissure, and lips. These areas need to be reconstructed as aesthetic units and each requires individualized management of donor tissue. The reconstruction of the burn patient is often a long process requiring multiple procedures. The approach presented here advocates a stepwise, prioritized approach aiming at both maximum function as well as optimal appearance.


Anti-Ro autoantibody with cross-reactive binding to the heavy chain of immunoglobulin G.

Autoantibodies directed at the intracellular Ro ribonucleoprotein complex are found in the serum of patients with systemic lupus erythematosus (SLE) and related autoimmune diseases. The antigenic stimulus for the induction of these autoantibodies is unknown, although we have previously demonstrated that the Ro protein and immunoglobulin G (IgG) share immunologic determinants bound by anti-Ro antibodies. The present study further defines the fine specificity of this cross-reactive binding. Using both patient autoanti-Ro antibodies and antigen-induced rabbit anti-Ro serum, the binding specificity for IgG was located to the heavy chains of IgG outside the Fc domain. F(ab')2 fragments of IgG were observed to inhibit specific Ro binding by either human or antigen-induced rabbit sera, while Fc fragments of IgG failed to inhibit Ro binding. Anti-Ro sera were found to bind the heavy chains of IgG in immunoblots, and the antibodies eluted from these heavy chains were capable of immunoprecipitating the Ro particle from human cell extracts. Not all patient sera with anti-Ro antibodies possessed IgG binding antibodies. Studies of cyanogen bromide digestion fragments of IgG implicate the hinge region of IgG as the region cross-reactive with the Ro protein. The nature of this cross-reactivity may be important in understanding the induction and/or perpetuation of the anti-Ro response in patients with autoimmune disease.


The pre-travel medical evaluation: the traveler with chronic illness and the geriatric traveler.

The pre-travel medical evaluation of elderly patients and patients with chronic illness requires special assessment and advice. Screening and special precautions are reviewed for traveling patients with respiratory disease, cardiac disease, sinusitis, diabetes mellitus, HIV infection, and other chronic medical conditions. Current guidelines for empiric therapy and prophylaxis of travelers' diarrhea are reviewed, with emphasis on concerns in geriatric or chronically ill travelers. Special considerations such as potential drug-drug interactions and insurance coverage are also discussed.


Malaria prophylaxis: taking aim at constantly moving targets.

The prevention of malaria infections is one of the most important functions that any clinician can perform for those traveling to tropical geographic regions where malaria risks are present. The prophylaxis question has become complicated by continued emergence of chloroquine-resistant strains of Plasmodium falciparum, the recent appearance of Plasmodium vivax resistance, and the availability of a wide choice of antimalarial pharmaceuticals. Chemoprophylaxis may produce different toxicities among various patient populations. With increasing numbers of women who travel during their professional lives, there are potential implications for using chemoprophylaxis during pregnancy. Children are unable to tolerate certain antimalarials because of toxicities unique for them. In some instances, the safest and most palatable formulations for children are not even available in the United States and must be purchased in Canada or elsewhere. Reliance upon chemoprophylaxis alone has proven to be increasingly futile. With the introduction of new repellent formulations and nontoxic insecticides for use on clothing or bed netting, there are non-pharmacologic adjunctive measures which can now be considered first-line for the prevention of malaria infections.


Current prevention and management of acute mountain sickness.

Acute mountain sickness was known to the Chinese in ancient times, as they traversed mountain passes between the Great Headache and Little Headache mountains into present-day Afghanistan. The Jesuit priest, Father Joseph Acosta, lived in Peru during the sixteenth century; he described both this syndrome and deaths which occurred in the high Andes. The incidence of high-altitude illness will rise as previously remote sites become more accessible to trekkers and skiers. Prevention and treatment are important concerns for those physicians who wish to advise their more adventuresome patients properly. This article incorporates a selected review of pertinent investigations, in the English-language literature over the past five years, into material previously presented at travel symposia for clinicians managing the prophylaxis and treatment of acute mountain sickness.


Evaluation of the returned traveler.

Recognition of clinical syndromes in returned travelers is an important part of providing care to international travelers. The first step is to take a history with attention to pre-travel preventive measures, the patient's itinerary, and potential exposure to infectious agents. The patient should then be examined to document physical signs, such as fever, rash, or hepatosplenomegaly, and to have basic laboratory data obtained. This evaluation will provide most physicians with the necessary information to generate a differential diagnosis. Each diagnosis should be matched against the incubation period of the disease, the geographic location of illness, the frequency of illness in returned travelers, and the pre-travel preventive measures. Careful attention to these aspects of patient care should result in the appropriate diagnosis and therapeutic intervention for the ill returned traveler.


[Further experiences with ovum lavage with respect to preventing premature labor].

Between January and December 1990, lavage of the ovum was performed in 64 gravidae with actual or potential symptoms of premature labour. Subsequently the lavage fluid was microbiologically examined. The present study discusses the indications for this new method, how it is performed and the results obtained. Microorganisms possibly necessitating treatment were detected in the lavage fluid of 30 (47%) of the gravidae at risk. Thirty-nine patients manifested actual symptoms of imminent premature birth, such as labour or critical cervical status. Results of fluid tests were positive in 23 (59%) of these patients, while according to the results of conventional cervical or vaginal smear tests performed simultaneously, treatment was necessary in only 13% of them. The majority of the microorganisms in the lavage fluid (coagulase-negative, haemolytic and group D streptococci were usually detected) are only facultatively pathogenic and are found in small quantities in cervical smears as normal "local flora". The mean delivery date was in gestational week (GW) 37/1, and for patients with antibiosis produced by a suitable antibiotic in GW 38/3 (10 weeks after lavage was performed). In view of the results of this study, bacteriological testing of ovum lavage fluid may be regarded as a useful complementary method for detecting ascending infections. It may advance pathogenetic research into late abortion and premature birth and further reduce the premature birth rate.


[Uses of vaginal pH measurement for prevention of premature labor. Results of a prospective study].

The influence of the microflora of the vagina and cervix has been undervalued for the induction of premature birth. Examination of the microbiological problem by determination of the vaginal pH in combination with the microflora (Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum). Report of the outcome of 161 prospective, ad the beginning normal pregnancies in comparison of 200 primary hospitalized pregnancies with symptoms of imminent premature birth. The vaginal pH is a very useful parameter of screening for identification of disturbances of the microflora in practice. In cases of pathologic pH (> 4.5) it is possible by therapy to reduce the premature birth rate.


[Detection of rupture of fetal membranes using a commercially available fibronectin test kit].

In a clinical examination an attempt was made to confirm the aptitude of a commercially available immunoassay to detect amniotic fluid. Pure amniotic fluid gained by amniocentesis, not mixed with other secretions, was used. On examination using three different batches the sensitivity of this test amounted to 35/55 in all, or 64%. We came to the conclusion that the present test was not sufficiently reliable to prove or disprove the discharge of amniotic fluid. An explanation is needed especially regarding the role played by the forces which occur during contractions and the presence of cervical and vaginal secretions when fetal fibronectin is found to be present. The evidence of fetal fibronectin could possibly become more important as a predictor of imminent labour than as being proof of the admixture of amniotic fluid in cervical and vaginal secretions.


[Does the "fatty pelvis" exist? Quantitative computer tomography studies].

50 Patients weighing between 45 and 114 kg underwent standardized computed tomography of the pelvis. Fat compartments from inside and outside of the small pelvis were assessed quantitatively by means of tracing the fat tissue borders and planimetry. Fat compartments within the small pelvis showed a rather weak correlation with body weight and the so called Rohrer-Index as a weight/height-Index, correlations with the latter being slightly better. From the fat compartments within the single levels the functional reduction of birth channel diameters caused by fat tissue was calculated for. The weight/height-index dependent increase of space demand within the birth channel was rather pronounced at the pelvic brim becoming slighter when reaching mid-pelvis or even pelvic outlet. Hence, the common assumption can no longer be maintained, that adiposity necessarily causes soft tissue dystokia due to larger fat compartments within the small pelvis.


[Comparison of the rate of complications after primary, secondary and emergency Cesarean section].

3799 women delivered by cesarean section at the Department of Obstetrics and Gynaecology of the University of Ulm between 1978 and 1988 were retrospectively divided into three groups, according to the urgency of cesarean section: group [1]: elective cesarean section (n = 1333), group [2]: urgent cesarean section (n = 2295), group [3]: emergency cesarean section (n = 171). Group [1] comprised the greatest risk in terms of maternal diseases, pregnancy complications and previous cesarean sections, group [2] the least. Intraoperative complications were seen more often in group [3] than in groups [1] and [2] and included a greater number of operations lasting more than 2 hours (group [3]: 2.3%, group [1] and [2]: < or = 0.5%), a higher incidence of severe blood loss and consequent need for blood transfusions, and of serious complications such as damage to adjacent organs and need for hysterectomy (group [3] 4.7%, groups [1] and [2]: 1.6%). In group [3] the rate of postoperative complications, especially of infections, was unexpectedly low (e.g. fever > 38 degrees C in group [1]: 8.6%, group [2]: 11.5%, and in group [3]: 9.9%). This was not only explainable by more frequent prophylactic use, in group [3], of antibiotics whose efficacy in reducing infections was demonstrated. Altogether five patients died, two deaths, both in group [2], were directly related to cesarean section. Between 1978 and 1988 an increasing incidence of low birth weight infants was found in all groups, with the highest rate in group [3].(ABSTRACT TRUNCATED AT 250 WORDS)


[Brain-specific creatine kinase (CKBB) in umbilical cord blood. A prognostic parameter in chronic intrauterine hypoxia?].

Elevated levels of brain type creatine isoenzyme (CKBB) have been demonstrated in serum after brain cell injury in neonates. A hypoxic lesion of the membrane permeability of the CKBB rich brain cells may lead to an increased enzyme leakage into the serum. As an increased release from the fetal brain as a result of intermittent compression and decompression of the fetal head during labour and after rupture of membranes may occur without hypoxic damage, only pregnancies which were terminates by cesarean section were studied. No mother went into first stage of labour and no rupture of membranes occurred. Three study groups were defined. The control group (elective cesarean section for breech presentation) showed CKBB enzyme activities below 15 U/l. A group with emergency cesarean sections had low CKBB values too, despite acidotic pH-values (pH < 7.20) at birth. The third group included fetuses which were delivered by cesarean section because of a pathological fetal heart rate tracing and intrauterine growth retardation. 6 out of 40 umbilical cord sera in this group showed elevated CKBB enzyme activities. If there was an additional fetal acidosis an increased neurological morbidity and neonatal mortality was seen.


[Three-dimensional analysis of the tunica media of umbilical arteries. Scanning electron microscopy study].

The three-dimensional media structure of the umbilical arteries in their various functional states has up to now been object of numerous investigations, which are predominantly based on light-microscopic findings and have come to extremely differing results. For that reason the electron microscope method with an optically higher resolution was chosen for this thesis. In total, 20 umbilical cords were recovered, and in each case one of the two umbilical cord arteries was kept in a condition of non-contraction by means of perfusion fixation immediately after the omphalotomy. After the necessary preparation longitudinal, diagonal and cross-sections of both non-contracted and fully contracted umbilical arteries as well as of the folds of Hoboken, which occur in the arteries postnatally, were investigated by the scanning electron microscope. During this examination the following findings were made: The media in the wide umbilical cord artery consists of two layers. The outer layer accounts for some three quarters of the wall and is composed of lamellae of parallel muscle fibres which surround the vessel alternatively in gently rising and falling thread-like turns. The inner layer accounts for the remaining quarter and also consists of lamellae the thread-like turns of which, however, run at a much higher pitch. Exactly subendothelial, a very thin layer of irregularly arranged fibres with longitudinal main direction can be clearly identified. The folds of Hoboken are caused by local media contraction in the course of which the outer media restructures itself, thus being the main carrier of the fold.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pathophysiology of cardiac arrhythmias].

Cardiac arrhythmias are ambiguous symptoms. Intracardiac as well as extracardiac alterations may be responsible. There is little direct information from the ECG concerning their pathophysiological mechanism. Bradycardic as well as tachycardic arrhythmias can be the result of two different fundamental disturbances: alterations of impulse formation (automaticity) or alterations of impulse conduction. Either one of these, or both of them acting together, may be responsible for the arrhythmia. Tachycardias due to disturbances of impulse formation may be brought about by enhanced firing of regular pacemakers (sino-atrial node, av-node, ventricular conduction system), by abnormal automaticity occurring in ordinary atrial or ventricular myocardium, or by triggered activity due to early or delayed afterdepolarizations. Bradycardic disturbances of impulse formation are primarily concerned with sino-atrial nodal function. Bradycardic conduction disturbances mainly impair sinoatrial or atrioventricular propagation causing partial or total conduction block. Tachyarrhythmias due to disturbances of conduction are generated by re-entry of excitatory waves either along anatomically preformed pathways or around functional obstacles (refractory zones) with excitable gaps being more or less pronounced. On the cellular level, altered activities of ionic channels or transport systems play a significant part. Such changes are caused by: alterations of electrolyte composition (potassium, sodium, calcium), acidosis or alkalosis, autonomic and hormonal influences, membrane active metabolites (long-chain acylcarnitine, lysophosphatidylcholine), drugs (class I and III antiarrhythmics, cardiac glycosides) and poisons. In disturbances of conduction other aspects like geometry of pathways or cable properties (anisotropic conduction, coupling resistances between cells) are of particular significance.(ABSTRACT TRUNCATED AT 250 WORDS)


[Principles for the classification of anti-arrhythmia agents in cardiac arrhythmias].

Clinically useful antiarrhythmic drugs are a group of heterogenous compounds, both with respect to chemical structure and to cellular mechanism of action. The classification of antiarrhythmic agents according to Vaughan Williams is based on electrophysiological findings in isolated heart muscle and defines four classes of drug actions. The criteria for classification include blockade of ion channels (classes I and IV), interaction with receptors (class II), and alteration of electrophysiological parameters, e.g., prolongation in action potential duration (class III). Several antiarrhythmic drugs possess actions in more than one class. The classification does not include all established antiarrhythmics, e.g., digitalis. Class-I action is further subdivided on the basis of extent of Na+ channel block and additional change in action potential duration. The kinetics of the onset and offset of Na+ channel block can be explained by models in which association and dissociation from the receptor are functions of channel state, i.e., activated, inactivated or resting. Detailed analysis has led to the concept of saturation block (24). Recently, the European Society of Cardiology has presented a classification of antiarrhythmics based on a more comprehensive compilation of drug action (18). Any useful classification of antiarrhythmic agents should offer guidance for their clinical use. This goal has not yet been reached. The criteria of classification are physicochemical properties or cellular mechanism of action as detected with sophisticated electrophysiological techniques. However, in spite of this fact, successful therapeutic use of antiarrhythmic drugs remains, to a large extent, still empirical.


[Evaluation of anti-arrhythmia agents in the animal model].

In view of the results of CAST, researchers working in the field of experimental arrhythmia have been increasingly focusing on the quest for new anti-arrhythmic modes of action and ways of detecting pro-arrhythmic properties of antiarrhythmic drugs at an early stage. Here, the experimental methods available play a particularly important role. While trying to assess anti-arrhythmic effects without investigating electro-physiological parameters in isolated tissue would be inconceivable, the degree to which the results of in vitro studies can be transferred to the intact organism is limited because of the complex nature of the arrhythmias. Of the various existing in vivo models, the most commonly employed are those in which arrhythmia is induced after experimental surgical interventions causing ischemia and infarction, followed by reperfusion. This shows that researchers are striving to "create" pathophysiologically-defined conditions and, as far as possible, a pathophysiological situation which is similar to that in the patient. Guidelines were laid down for this model complex in the Lambeth Conventions (1988) in order to improve uniformity of the methods and better comparability of the results generated by different investigators. Of the existing arrhythmia models, the ventricular re-entry arrhythmia model after myocardial infarction triggered by programmed stimulation, which was devised by Spear/Moore (1983), has proven to be particularly useful in the assessment of antiarrhythmics and is used by many researchers. Class II and III antiarrhythmics can be identified reliably by this method, whereas class I antiarrhythmics are mostly inconspicuous.(ABSTRACT TRUNCATED AT 250 WORDS)


[The pro-arrhythmia effects of anti-arrhythmia agents--theoretical and clinical aspects].

Proarrhythmic action of an antiarrhythmic drug is defined as 1) Worsening of preexisting arrhythmia (for example, increase of number of premature beats; frequency, rate, and duration of tachycardias at supraventricular or ventricular level); 2) induction of arrhythmias (supraventricular: for example, atrial tachycardia with block; ventricular: monomorphic or polymorphic ventricular tachycardia, torsade de pointes, ventricular fibrillation); 3) occurrence of bradycardia (sick sinus syndrome; atrioventricular and intraventricular conduction disturbances). The pathophysiology of proarrhythmic action is either facilitation of conduction block and reentry, or abnormal impulse formation. Induction of incessant monomorphic ventricular tachycardia or torsade de pointes is of special clinical relevance. Incessant ventricular tachycardia can be experimentally explained by an increase of functional conduction block and decrease of the wavelength of excitation (conduction velocity x refractory period) as actions favoring reentry; this is clinically most frequently seen with the application of class IC (and A)-drugs. Abnormal QT prolongation and torsade de pointes are most likely due to early afterdepolarizations of the cell membrane, and development of triggered activity; these arrhythmias are seen following the application of substances prolonging repolarization (class III and class IA-antiarrhythmic drugs). Independent of the precise electrophysiologic mechanism, arrhythmias may, under clinical conditions, also be provoked secondary to the negative inotropic action of these drugs. Proarrhythmic actions most frequently are concentration-dependent; rarely are they idiosyncratic. Usually, these side-effects are seen during the first days after initiation or increase of the antiarrhythmic drug dose; they may, however, manifest themselves only after a couple of months.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical evaluation of new anti-arrhythmia drugs after the CAST (Cardiac Arrhythmia Suppression Trial) study].

The results of the Cardiac Arrhythmia Suppression Trial (CAST) are of great importance for the development and clinical evaluation of new antiarrhythmic agents. Today, the development of a new antiarrhythmic drug is only justified, if the benefit risk ratio is superior compared to those agents already available in clinical practice. The primary criterion of therapeutic efficacy is the prevention of tachyarrhythmic sudden cardiac death and/or the prevention of sustained ventricular tachycardia.


[Ventricular cardiac arrhythmias 1992. Summary and perspectives].

The treatment of tachycardias has undergone marked changes. Doubts on the effectiveness and the benefits of antiarrhythmic drug therapy are the reason for a re-evaluation of the use of so-called class I- and class III-antiarrhythmic drugs. At the same time, there has been an increased awareness of new techniques for risk assessment; for instance, in postmyocardial infarction patients, not only the type and frequency of spontaneous arrhythmias but also other parameters like extent of left ventricular dysfunction, ventricular late potentials, inducible ventricular arrhythmias and effects of the autonomous nervous system should be considered. Serial electrophysiological testing to predict the efficacy of antiarrhythmic drug therapy has recently been challenged. Non-pharmacological approaches have been used in an increasing proportion of patients. Nevertheless, there is also an increasing interest in new antiarrhythmic drugs, especially those that prolong repolarization (class III).


[Biochemical changes and disorders of electromechanical coupling in chronic heart failure].

In the chronically failing heart, subtle biochemical alterations occur at the level of a number of subcellular systems. The cellular elements that control activation and inactivation of the contractile proteins are the plasma membrane and the sarcoplasmic reticulum (SR). During the plateau phase of the action potential the slow calcium channel is activated so that calcium ions enter into the interior of the cell and initiate--as a trigger signal in loco--the calcium release from the SR-calcium-stores. In the absence of catecholamines the measured calcium ion currents are similar when normal human myocardium is compared to end-stage failing human myocardium. However, the increase in the calcium ion currents induced by maximum concentrations of catecholamines is significantly smaller in failing myocardium compared to normal myocardium. This observation can easily be explained by the down-regulation of the beta-1-adrenoceptors and the increase in the inhibitory Gi-proteins. In the failing myocardium, therefore, a beta-1-adrenoceptor stimulation leads to an insufficient increase in cyclic adenosine monophosphate so that the opening probability of the calcium channels is not appropriately enhanced. This results in a decreased contractile reserve. As far as is known today, the inactivation mechanisms of the plasma membrane (sodium-calcium-exchanger, sodium-potassium ATPase, calcium ATPase) are not disturbed in the failing human myocardium. The calcium release from the SR can be quantified using either calcium indicators (aequorin, fura 2) or highly sensitive thermopiles. Both sophisticated heat measurements and fura-2 measurements indicated a decreased systolic calcium ion concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical pharmacology of acetylsalicylic acid].

The pharmacological actions of acetylsalicylic acid (ASA) are determined by two compounds: ASA and salicylic acid. Salicylic acid is formed from its precursor ASA within 15-20 min after oral application and is responsible for the antiinflammatory, antipyretic, and analgetic activities of ASA. However, the platelet inhibitory, i.e., the antithrombotic action of ASA is only due to this compound itself and is caused by irreversible inhibition of the platelet cyclooxygenase, i.e., inhibition of thromboxane A2 formation. The bioavailability of plain ASA after oral administration amounts to 40-50% at therapeutic doses. This is due to rapid deacetylation prior to reaching the systemic circulation. This deacetylation accounts for a significant part of inhibition of platelet cyclooxygenase within the portal circulation which is further enhanced by using sustained-release preparations. Doses of 40-50 mg ASA per day are sufficient to maintain complete blockade of platelet cyclooxygenase and this agrees well with the established efficacy of 75 mg ASA/day in controlled clinical trials on secondary prevention of myocardial infarction.


[Acetylsalicylic acid in unstable angina, after coronary revascularization and in prevention of cardiac thromboembolism].

Acetylsalicylic acid (ASA) inhibits platelet function via cyclooxygenase inhibition. The selective inhibition of platelet cyclooxygenase is possible with the use of low doses of ASA due to presystemic acetylation of the platelet enzyme in the portal circulation. The clinical efficacy of ASA has been demonstrated for a number of indications. ASA reduces the rate of myocardial infarctions and cardiovascular deaths in patients with unstable angina. Simultaneous intravenous infusion of heparin has an additional positive effect. The prevention of acute coronary thromboses during PTCA and of early bypass graft occlusion has been convincingly demonstrated, if therapy is initiated immediately after surgery. Neither ASA nor any other drug has been effective in the prevention of late restenosis following PTCA and of late bypass graft occlusions. Thromboembolic complication after implantation of biological valve prostheses is significantly reduced by ASA, if no rheumatic valve disease is present. The rate of peripheral or cerebral thromboembolic events is markedly increased in patients with lone atrial fibrillation. In contrast to the very positive results obtained for anticoagulants, the reports with ASA were contradictory. ASA may be effective in preventing thromboembolic complications in younger patients with a lower risk or in elderly patients with contraindications for anticoagulation. For most clinical indications the efficacy of ASA has been demonstrated for doses of 75-324 mg/d. Following a loading dose of 300 mg on the first day, continuation of therapy with 100 mg/d should combine maximal therapeutic efficacy with a low rate of unwanted drug effects.


[Thromboxane A2 and prevention of cardiovascular diseases].

Thromboxane A2 (TxA2) is the main arachidonic acid metabolite in human platelets and exhibits two major activities; stimulation of platelet function, including secretion of platelet-derived storage products, e.g., 5-HT, PDGF, and vasoconstriction. Platelet hyperreactivity is typical for advanced stages of atherosclerosis and is paralleled by elevated circulating thromboxane levels. This is the target for TX-antagonistic compounds. Three classes of selective compounds are available: inhibitors of thromboxane synthase, antagonists of thromboxane receptors, and mixed-type agents. Positive experimental data with all of these compounds are available. However, clinical experience is limited and, in general, not convincing. This review discusses possible reasons for that and suggests that, in particular, the use of combined-type agents as antithrombotics may be superior to acetyl-salicylic acid in several forms of ischemic cardiovascular diseases.


[Prevention of cardiovascular diseases by intervention in lipid metabolism].

Atherogenesis is a multifactorial event. Experimental, clinical and epidemiological studies, however, have clearly indicated the major role of LDL-cholesterol in the process of cholesterol deposition in the arterial wall. Although most patients with severe hypercholesterolemia suffer from premature coronary heart disease, it is a medical experience, that there are subjects who tolerate hypercholesterolemia and reach high ages without problems of their coronary arteries. Thus, there is much biological variation in the response of the arterial wall to elevated LDL-cholesterol, a fact which emphasizes the need to differentiate between goals and means of primary and the goals and means of secondary prevention of coronary heart disease and between the goals of a population strategy and the goals and means of an individual therapeutic strategy. Today the knowledge about the role of lipids and lipoproteins in atherogenesis is convincing. Epidemiological as well as intervention studies have proven the benefit of an appropriate lipid lowering therapy.


[Prevention with vasoactive drugs].

Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also to improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine (also under clinical conditions) if coronary flow reserve can be improved, in 30 hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with an ACE-inhibitor (enalapril 10-20 mg/d), a calcium channel blocker (diltiazem 120-180 mg/d) and a beta 1-selective beta-receptor-blocker (bisoprolol 5-10 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a comparable decrease in LV muscle mass, coronary reserve was improved after enalapril by 48%, after diltiazem by 48%, and after bisoprolol by 22%. It is possible that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities on the level of the coronary microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)


[Prevention with angiotensin-converting enzyme (ACE) inhibitors].

Preventive therapy by angiotensin-converting-enzyme (ACE) inhibitors is considered in hypertension and, more recently, in chronic heart failure. The mechanism of action of ACE-inhibitors is complex; most extensively studied, however, is their inhibitory effect on angiotensin-II production. ACE-inhibitors may act as vasodilators, reducing pre- and afterload. On the other hand, local renin-angiotensin systems may control growth processes both in myocardial and in smooth muscle cells. This may be another site of action for ACE-inhibitors. ACE-inhibitors are reliable antihypertensive drugs and may have additional specific effects on the heart and vascular smooth muscle. Clear evidence is, however, missing for their superiority above other drugs in preventing cardiovascular complications of hypertension. Most recently, the data of the "study of left-ventricular dysfunction" (SOLVD) and "survival and ventricular enlargement" (SAVE) study became available. These studies showed that ACE-inhibitors could prevent the incidence of heart failure in about one-third of patients with severe left-ventricular dysfunction during 3 years of observation when compared with placebo treated patients. A new indication, therefore, for ACE-inhibitors could be left ventricular dysfunction after myocardial infarction. It remains unclear 1) what could be the adequate diagnostic procedures to identify patients for preventive treatment, 2) when therapy should be started, 3) about the duration of therapy, 4) about the doses of ACE-inhibitors for this indication, 5) what will be the side-effects when used in a broader population, and 6) will this prevention of heart failure be a specific effect of ACE-inhibitors?


[Pharmacologic prevention of cardiovascular diseases with calcium antagonists].

The major impact of calcium-antagonists in prevention strategies of cardiovascular disease evolves from their modulation of signal transduction and metabolic processes controlled by calcium-ions as "second messenger" in cells participating in the early development of vascular atherosclerotic lesions, namely endothelial cells, vascular smooth muscle cells, monocytes/macrophages, T-lymphocytes and platelets. In accordance with experimental data suppression of angiographically early coronary lesions was documented in four independent clinical studies using quantitative analysis of repeated coronary angiography: Nifedipine and Nicardipine reduce angiographically "new" (minimal) lesions to 30-70%, in some cases already after 1 year of treatment. This anti-atherosclerotic effect is independent of known risk factors and indicates a new strategy in "primary" prevention of atherosclerotic vascular disease. In pre-infarction-syndromes calcium-antagonists demonstrate a tendency in attenuating anginal symptoms and progression into definitive infarction. Analysis of studies in acute infarction showed a neutral effect of calcium-antagonists with unchanged infarct-size, regional and global ventricular function or early mortality. In post-infarction patients only strict selection criteria (up to 60% of patients) as well as delayed onset of therapy (> 7 days after infarction) reduce the number of re-infarction and mortality. Subgroup analysis indicate that calcium antagonists with mild afterload reduction and minimal negative inotropic impact might be preferable. The suppression of "early" lesions should be regarded as the predominant benefit for future strategies in prevention of cardiovascular disease with calcium-antagonists.


[Changes in gene expression in terminal myocardial failure].

End-stage human heart failure is the common final manifestation of a group of heterogeneous diseases, and it is usually accompanied by myocardial hypertrophy. Studies on animal models have shown that myocardial hypertrophy is an adaptational process accompanied by characteristic changes in the expression of cardiac genes: reinduction of fetal isoforms of the myofilaments actin and myosin, downregulation of SR Ca(2+)-ATPase and phospholamban, downregulation of beta-adrenoceptors and increased expression of inhibitory G proteins (Gi). These alterations lead to reduced shortening velocity, slowed relaxation, and to desensitization of adenylyl cyclase, thereby probably increasing myocardial economy and lowering energy demand. Gene expression in human end-stage heart failure due to dilated cardiomyopathy exhibits some clear differences, but also significant parallels to gene expression in experimental hypertrophy: there is no isoform shift because fetal isoforms of the myofilaments are already predominant in the adult ventricle. However, like in animal models expression of SR Ca(2+)-ATPase and phospholamban is decreased, correlating with slowed relaxation of the diseased myocardium, beta-adrenoceptors are downregulated, and the expression of Gi is increased, leading to desensitization of the adenylyl cyclase pathway. These results suggest that alterations of gene expression in human end-stage myocardial failure, known so far, are secondary to chronic overload and are not a primary cause in the pathogenetic process. They are probably initially favorable adaptive processes to chronic overload, but finally cause a further deterioration of contractile performance of the myocardium.


[The significance of myocardial hypertrophy in heart failure].

Myocardial hypertrophy in response to elevated myocardial wall stress largely results from myocyte hypertrophy. In congestive heart failure, this hypertrophy can have compensatory as well as critical relevance. On the one hand, it reduces myocardial wall stress in the case of hemodynamic overload by enhancing ventricular wall thickness. On the other hand, risks and problems may result from the tissue changes associated with myocardial "overload-hypertrophy", such as alterations in myocyte phenotype, augmentation of connective tissue in the myocardium, reductions in coronary reserve (even without altherosclerotic coronary stenoses), and alterations in the local formation of growth cofactors (i.e., enhanced myocardial expression of angiotensinogen and converting enzyme). Changes in myocyte phenotype occur in receptor signal transduction, in isoform shifts of contractile proteins and of key enzymes in energy metabolism towards a more fetal-like pattern, and in a "fragility" of Ca(++)-homeostasis (due to reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and enhanced expression of membrane Na+/Ca(++)-exchange in presence of maintained density of Ca(++)-channels). Additionally, the fraction of contractile fibers and mitochondria per myocyte cross-section can be reduced with attenuated systolic function. The fragility of Ca(++)-homeostasis must be regarded as potentially critical because of retarded inactivation of contraction and because of susceptibility to diastolic Ca(++)-overload with delayed after-depolarizations. Additionally, diastolic dysfunction may result from interstitial fibrosis and ischemia due to reduced coronary reserve (altered vascular structure and endothelial dysfunction).(ABSTRACT TRUNCATED AT 250 WORDS)