Right ventricular cardiomyopathy and sudden death in young people

From 1979 to 1986, we conducted postmortem studies of 60 persons under 35 years of age who had died suddenly in the Veneto Region of northeastern Italy. Unexpectedly, we found that 12 subjects--7 males and 5 females ranging in age from 13 to 30 years--had morphologic features of right ventricular cardiomyopathy. This disorder had not been diagnosed or suspected before the subjects died. In five cases, sudden death was the first sign of disease; the remaining seven subjects had a history of palpitation, syncopal episodes, or both, and in five of those seven, ventricular arrhythmias had previously been recorded on electrocardiographic examination. Ten of the subjects had died during exertion. At autopsy, the subjects' heart weights were normal or moderately increased. Two main histologic patterns were identified--a lipomatous transformation or a fibrolipomatous transformation of the right ventricular free wall (6 cases each); in all cases, the left ventricle was substantially spared. Signs of myocardial degeneration and necrosis, with or without inflammatory infiltrates, were occasionally observed. These findings indicate that right ventricular cardiomyopathy, the cause of which is still unknown, may be more frequent than previously thought. At least in this area of Italy, it may represent an important cause of sudden death among young people.     

Duplication of distal 22q

We report on three patients with duplication of distal 22q. One patient is a de novo carrier of the translocation t(21;22) (p13;q11), the other two are offspring of a translocation carrier t(10;22) (q26;q12). The clinical manifestations of these patients demonstrate the variability of the dup(22q) syndrome.     

Evaluation of toxic effects following administration of monoclonal antibody MBr1 in patients with breast cancer

Twelve patients with disseminated breast cancer were injected with monoclonal antibody MBr1 at the National Cancer Institute of Milan, Italy, from January 1983 to March 1985. The first seven patients had advanced disease and the remaining five operable breast cancer. In the first seven patients the initial dosage of MBr1 was 0.5 mg and was doubled in the next patient up to 16 mg. The last five women received 10 mg of MBr1. No general side effects such as bronchospasm, hypotension, immediate or delayed allergic reactions were observed. Four patients who were injected with 10 mg or more experienced fever, shudder and vague abdominal and articular pain. The following tests were monitored: R.B.C., W.B.C., percentage of lymphocytes, blood glucose, urea nitrogen and creatinine, serum levels of Na+, K+, Cl-, total proteins levels, albumins and globulins, bilirubin, GOT, GPT, alkaline phosphatase, LDH, amylase, gamma GT and CPK. No major modifications were observed: a limited increase of the transaminases, LDH and gamma GT was evident at the last check. An early temporary alteration of CPK was observed in the four patients who had symptoms. Serum levels of MBr1 are detectable immediately after injection starting from 4 mg, and all sera were negative 48 hours later. It is concluded that the scanty toxicity allows to continue clinical investigations to verify the linkage between MBr1 and Ca-MBr1 "in vivo" after a single injection of no more than 16 mg of the MoAb. The increase of this dosage as well as multiple injections do not seem safe at present.     

Induction of mixed function oxidases by petroleum in the American eel,Anguilla rostrata

American eels,Anguilla rostrata, were exposed to crude oil by ingestion of a 10, 100, or 500 l/kg fish dose per day for five days. Depuration was followed for an additional twelve days. All oil doses caused an induction of hepatic microsomal enzymes, maximally by three days of exposure. Benzo(a)pyrene hydroxylase (BaPH) showed a dose related response, with greater induction at 100 l/kg than at the other doses. The highest dose was hepatotoxic. Cytochrome P-450 induction was dose independent, and remained induced maximally for the entire experimental period, in contrast to BaPH which declined in activity. Reaction optimum for BaPH was at pH 7.5 and 27°C. A study of tissue distribution showed the liver to account for nearly all BaPH activity. A significant increase in the protein content of the hepatic postmitochondrial fraction of oil-exposed fish was also observed.     

Magnetic resonance imaging measurements of the response of murine and human tumors to the vascular-targeting agent ZD6126.

PURPOSE: ZD6126 is a novel vascular targeting agent currently undergoing clinical evaluation. It acts by destabilizing the microtubulin of fragile and proliferating neoendothelial cells in tumors. The drug leads to blood vessel congestion, the selective destruction of the vasculature, and extensive necrosis in experimental tumors. The aim of the study reported here was to assess the ability of dynamic contrast enhanced magnetic resonance imaging (MRI) to measure the antivascular effects of ZD6126 in tumors. EXPERIMENTAL DESIGN: The work was carried out in mice bearing C38 colon adenocarcinoma and in patients with advanced cancers. MRI was performed before and 6 h (human tumors) or 24 h (C38 tumors) after i.v. drug administration. Contrast agent (gadolinium diethylenetriaminepentaacetate) enhancement was characterized by the initial area under the gadolinium diethylenetriaminepentaacetate uptake versus time curve (IAUC). IAUC reflects blood flow, vascular permeability, and the fraction of interstitial space. RESULTS: The median IAUC was reduced in all C38 tumors after ZD6126 administration [by 6-48% at 50 mg/kg (n = 3)], 58-91% at 100 mg/kg (n = 4), and 11-93% at 200 mg/kg (n = 6). In contrast, the administration of vehicle only led to no consistent change in median IAUC (n = 4). The ZD6126-induced changes in median IAUC appeared to be dose dependent (P = 0.045). No ZD6126-induced changes were apparent in murine muscle. Similar effects were seen in preliminary data from human tumors (11 tumors studied, 9 patients). At doses of 80 mg/m(2) and higher, the median IAUC post-ZD6126 treatment was reduced in all of the tumors studied (8 tumors, 6 patients) to 36-72% from the baseline value. There was a significant trend of increasing reductions with increasing exposure (P < 0.01). No drug-induced changes in human muscle or spleen IAUC were apparent. The reproducibility of the median IAUC parameter was investigated in patients. In 19 human tumors (measured in 19 patients) inter- and intratumor coefficients of variation were 64 and 18%. CONCLUSIONS: The contrast enhanced-MRI measured median IAUC is a useful end point for quantifying ZD6126 antivascular effects in human tumors.     

Ablación de taquicardia ventricular asistida con ECMO. Primera experiencia en nuestra institución

Catheter ablation is useful for reducing drug refractory ventricular tachycardia (VT) episodes and can be life-saving when VT is incessant or arrhythmic storm. Left ventricular hemodynamic support may be required in patients with VT and hemodynamic instability. Extracorporeal membrane oxygenation (ECMO) support is an alternative to achieve ventricular tachycardia mapping and ablation over long periods of time. We present a case of successful catheter ablation of substrate in a patient with ischemic heart disease and ventricular tachycardia with hemodynamic instability performed using venous- arterial ECMO support. There were not episodes of ventricular tachycardia after 2 years of follow-up.     

Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum: A case report

Rationale:Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication.Patient concerns:We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization.Diagnoses:Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern.Interventions:Hydration with glucose 5% solution, pantoprazole and vitamin K were administered, meanwhile other causes of hepatitis were ruled out and the ongoing antibiotic treatment was stopped suspecting a drug-induced liver injury.Outcomes:Liver function nearly completely recovered 1 month later with a first rapid improvement, within few days, of aminotransferases and coagulation studies, and slower of cholestatic enzymes.Lessons:We describe the first case available in the literature of hepatotoxicity associated with metronidazole treatment in a xeroderma pigmentosum patient. Clinicians therefore, based on this report and according to the possible underlying mechanism shared by other genetic diseases characterized by alterations in the pathway of DNA-repair, should consider such adverse event also in patients affected by this rare disease.     

Nonoliguric hyperkalemia in the premature infant weighing less than 1000 grams

Eighteen very low birth weight premature infants born before 28 weeks gestation and weighing less than 1000 gm were evaluated prospectively for disturbances in serum electrolyte concentrations and for renal glomerular and tubular functions. Clinically symptomatic hyperkalemia resulting in significant electrocardiographic dysrhythmias developed in eight of these infants; 10 babies remained normokalemic. Peak serum potassium concentration ranged from 6.9 to 9.2 mEq/L in the hyperkalemic group; all potassium values in the normokalemic group were less than 6.6 mEq/L. Indices of renal glomerular function and urine output were similar in both groups; no infant had oliguria. Serum creatinine concentrations were the same in both groups (1.04 +/- 0.16 SD mg/dl in normokalemic vs 1.19 +/- 0.24 mg/dl in hyperkalemic infants, beta less than 0.2 at alpha = 0.05), and glomerular filtration rates did not differ significantly (6.29 +/- 1.78 ml/min/1.73 m2 in normokalemic vs 5.70 +/- 1.94 ml/min/1.73 m2 in hyperkalemic infants, beta less than 0.2 at alpha = 0.05). In contrast, indicators of tubular function revealed a significantly larger fractional excretion of sodium in hyperkalemic infants: 13.9 +/- 5.4% versus 5.6 +/- 0.9% in normokalemic control subjects (p less than 0.001). Hyperkalemic infants also had a tendency toward lower urine concentrations of potassium, although there was no significant difference in their net potassium excretion in comparison with that in the normokalemic group. We speculate that hyperkalemia in the tiny baby is in part the result of immature distal tubule function with a compromise in ability to regulate potassium balance.     

Meningococcal meningitis with ‘normal’ cerebrospinal fluid

A prospective study was made of all patients with normal CSF counts and positive cultures for Neisseria meningitidis diagnosed in “El Vallés” County, Barcelona between January 1987 and December 1990. Meningococcal meningitis was documented in 82 patients, eight of whom (seven children, five boys and two girls with a mean age of 5·6 ± 3·3 years, and a 69-year-old male patient) had no apparent CSF abnormalities in the initial lumbar puncture. At the time of admission all patients had fever (mean 39·1 °C) of 10·8 ± 5·6 hour duration and petechial rash which had been present for a mean of 3·6 ± 3·3 hours. Signs of meningeal irritation were not found. A 4-month-old infant with symptoms of circulatory collapse, intracranial hypertension and impairment of consciousness subsequently died of septicemia in 48 hours. Group B N. meningitidis was isolated in six cases (reduced penicillin-susceptibility in two cases) and group C N. meningitidis in the remaining two (reduced penicillin-susceptibility in one case). Patients without pleocytosis did not differ in a statistically significant fashion from the patients with high pleocytosis in the duration of temperature, and petechial rash, leukopenia, positive blood culture and fatal outcome.