Bioavailability and Pharmacokinetics of a New Sustained-Release Potassium Chloride Tablet

The bioavailability of a new sustained-release potassium chloride (KC1) tablet, designed for once-a-day dosing, was compared to a KC1 elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P < 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KC1 elixir dosed 6 hr apart.     

Early bladder outlet obstruction in fetal lambs induces renal dysplasia and the prune-belly syndrome

A model of posterior urethral valves in fetal lambs was developed in order to evaluate the effect of intrauterine urinary obstruction on the developing kidney. Complete urethral obstruction was induced in five fetal lambs at 43 to 45 days of gestation. Two control fetal lambs underwent sham operations. At full term (140 days), two of the five experimental lambs and both control lambs were available for postmortem examination. Results of gross and histological examination of the control lambs were normal. In contrast, the kidneys of the experimental lambs were markedly asymmetrical in size. Histological examination of the kidneys in experimental lambs showed cystic dilatation of the collecting ducts and occasional cystic dilatation of Bowman's spaces, features compatible with obstruction. Also noted were peripheral cortical cysts and primitive tubules lined with cuboidal epithelium and surrounded by fibromuscular collarettes, characteristic of renal dysplasia. One of the infant lambs had many characteristics of the prune-belly syndrome, including a wrinkled, markedly distended abdomen, deficient abdominal wall musculature, flared chest wall, limb deformities, and undescended testes. These results suggest that early in utero urethral obstruction (at the beginning of the second third of gestation) causes renal dysplasia. The results also support the hypothesis that the prune-belly syndrome results from abdominal distention that occurs early in gestation.     

Using polymerase chain reaction to human papillomavirus in oral and pharyngolaryngeal carcinomas

Purpose: Increasingly, evidence has shown that human papillomavirus (HPV) plays a role in the induction of certain carcinomas. The presence of HPV sequences in 56 previously untreated oral and pharyngolaryngeal carcinomas was examined by the polymerase chain reaction (PCR).Materials and Methods: After DNA extraction, samples underwent 40 replication cycles with specific oligonucleotide primers corresponding to sequences from the E6 open-reading frame of HPV-6b, HPV-16, and HPV-18. To determine the E6 genomic integration, positive samples were processed with specific primers for the corresponding HPV L1 genes. Genomic HPV DNA cloned into PBR 322 was used as positive control.Results: HPV E6 DNA of the 6b and 16 types was detected in 14 patients (25%). The L1 gene was not present.Conclusion: Detected HPV E6 DNA might be integrated into the cell genome in the positive cases as indicated by the absence of the L1 gene-coding for the viral capside. Histological and clinical parameters, such as tumor location, degree of differentiation, stage, recurrence, and survival rates, were unrelated to the presence of HPV.     

Bladder cancer and asbestos in Spain

The relationship between bladder cancer and occupational exposure to asbestos was investigated between 1978 and 1982 at La Paz Hospital in Madrid in a case-control study conducted among 353 male patients and 53 women with a diagnosis of urothelium carcinoma, and among an equal number of controls matched in age (decade of life), sex and date of admission to the hospital. The results showed that bladder cancer is associated with occupational exposure to asbestos.     

The Rigiflex TTS: A New Method to Dilate Benign Esophageal Stenosis

Abstract: This paper dicusses the use of esophageal dilatation with a Rigiflex TTS balloon. This method was used 45 times on 11 patients affected by anastomotic or a severe grade peptic esophageal stenosis. Fluoroscopic guidance was used in 36 procedures (80%) without effecting the mean duration of the treatment (12 minutes). The results were considered satisfactory when these goals had been achieved: a) dilatation of the stenosis over 15 mm; b) a dysphagia free-time of more than 6 months. A satisfactory result was achieved in 10 patients (90.9%), without deaths and major complications. 5 patients received 1 dilatation and the other 5 needed, 3-3-4-7–11 procedures respectively to obtain a satisfactory result. On these basis we consider that its great efficacy, security and tolerability depend on the following characteristics of the Rigiflex TTS balloon: 1) “radial” dilatation; 2) the possibility of introducing the balloon through the operative channel of the fiberscope; 3) direct visualization of the stenosis during dilatation. The following disadvantages with this method are: the absence of a tactile sensation of dilatation and the elevated cost of the instrument. We conclude that the Rigiflex TTS balloon is an important alternative to guide-wire techniques, especially for the treatment of severe esophageal strictures.     

Lofepramine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness

Lofepramine is a tricyclic antidepressant that is structurally similar to imipramine and is extensively metabolised to desipramine. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from the facilitation of noradrenergic neurotransmission by uptake inhibition, and possibly by the additional facilitation of serotoninergic neurotransmission. The overall therapeutic efficacy of lofepramine is comparable to that of imipramine, amitriptyline, clomipramine, maprotiline and mianserin in patients with depression of varying severity, and coexisting anxiety. Dry mouth is the most commonly reported side effect of usual therapeutic doses of lofepramine, but the incidence of this and other anticholinergic side effects is less among patients treated with lofepramine than with imipramine. Lofepramine has not been associated with adverse effects on cardiac function even in cases of attempted suicide by overdose. Thus, providing its apparent favourable side effect profile is confirmed in practice, lofepramine may be a valuable alternative for treatment of the depressed patient where a tricyclic is indicated.     

Carcinoma of the prostate with atypical immunohistological features. Clinical and histologic correlates

In seven patients with undifferentiated carcinoma of the prostate, the immunohistochemical stain for prostate-specific antigen was negative. The stain for prostatic acid phosphatase done on the same tissue samples was diffusely positive in three, focally positive in three, and negative in one. Only the three with diffusely positive immunostaining had elevated serum acid phosphatase levels, although five had evidence of metastatic disease. All seven neoplasms were histologically similar, being composed of large cells with large nuclei, a moderate amount of cytoplasm, and indistinct cell borders. All tumors grew as broad sheets within the prostatic stroma as well as in the prostatic urethra; in six cases. Thus, prostatic carcinoma with this histologic pattern frequently loses prostate-specific antigen immunoreactivity. Awareness of this occurrence should prevent a misdiagnosis of urothelial carcinoma in such cases. The prostatic origin of these neoplasms can usually be verified by prostatic acid phosphatase immunostaining, which proves to be more sensitive in this particular setting.