Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.     

Acquired renal cystic disease: two cases of associated adenocarcinoma and a renal ultrasound survey of a peritoneal dialysis population

Long-term dialysis patients frequently develop acquired renal cystic disease (ARCD). The discovery of ARCD and renal cell carcinoma in one of our hemodialysis patients led us to review the literature. ARCD has been described mainly in the maintenance hemodialysis (MH) population. Therefore, we investigated 20 peritoneal dialysis (PD) patients for ARCD using ultrasonography. Seven patients (35%) had detectable cysts and two patients (10%) had multiple bilateral cysts. One patient had a large asymptomatic complex cyst that proved to be an adenocarcinoma. Our study suggests that ARCD is relatively common in the PD population, and we speculate that it may be related more to length of time in end-stage renal disease (ESRD) than to the mode of dialysis. The potential for malignant change appears to justify a routine screening examination with ultrasonography and/or computerized tomography (CT) to detect this recently described and probably underrecognized entity.     

Chronic obstructive pulmonary disease with tracheostomy: report of case involving endodontic treatment

Modern medicine has made many advances in the capability to sustain life. The dental profession needs to keep up to date with these changes and be creative in caring for these individuals who are medically compromised and who require special care.¹¹ This sometimes requires the purchase of new equipment; other times it means modifying that which exists. In all instances, the level of care for these individuals requires a team approach and mandates education of all team members. In the case presented, the medical problems necessitated such a team effort to achieve optimal care.     

Renal magnesium wasting in two families with autosomal dominant inheritance

Hypomagnesemia due to isolated renal magnesium loss was demonstrated in two unrelated families with autosomal dominant mode of inheritance. Magnesium infusions performed in two patients showed not only a reduced renal magnesium threshold but also a lowered renal tubular maximum for magnesium. All members of both families who presented with hypomagnesemia had also a lowered excretion of calcium in the urine, presumably as a consequence of increased reabsorption in Henle's loop.     

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Use of Telemetered Electrograms in the Assessment of Normal Pacemaker Function

The facility of direct real-time endocardial electrogram recording offered by newer pacemaker models can be helpful in the assessment of normal pacemaker function. Confirmation of the main hallmarks of sensing (amplitude, slew rate, and timing of the electrogram) can be achieved. Assessment of pacing capture also can be made; techniques for further analysis using external signal averaging can enhance this. The measurement of atrial and ventricular electrograms by telemetry has led to alterations in the protocol used at implantation to allow for the input impedance of the sensing circuit of the pacemaker. Accurate measurements of retrograde VA conduction times and confirmation of normal upper rate limit behavior of ODD pacemakers can be achieved simply and reliably using telemetered electrograms from the permanent pacemaker system.     

Worldwide epidemiology and modes of transmission of delta hepatitis

Conclusions Since the discovery of HDV in 1977 byRizzetto and collegues (10), several studies regarding the pathogenesis, natural history and epidemiology of this infection have been accumulated. It emerges that HDV is an agent with unusual biologic properties which requires HBV replication for its expression. Given the obligatory association between HDV and HBV, transmission of HDV follows the same routes of HBV transmission. This implies that one expects HDV infection to be much more prevalent in countries with high HBsAg carrier rates. This is true in most areas of the world but not in Far East Asia. Endemicity of HDV is maintained in the community through the network of HBsAg carriers. HDV can be transmitted to HBV positive and negative individuals, but survives only after encountering the carrier. Recent outbreaks of severe epidemics of fulminant hepatitis due to HDV among the Yucpa Indians in Northern Venezuela, pointed out very clearly that HDV superinfection is an ominous risk for all populations where HBV is endemic.