Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-Infected Children

We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (± standard deviation) in the children was 0.53 ± 0.19 liter/kg/h (229 ± 77 ml/min/m² of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 ± 0.18 and 2.2 ± 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% ± 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 μM for ≥8 h of 24 h on the twice daily oral dosing schedule with doses of ≥2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.     

Presence of synaptonemal complex protein 1 transversal filament-like protein in human primary spermatocytes

The synaptonemal complex (SC) is involved in the pairing of chromosomes during meiosis. We found that antibodies raised against a protein component (P1) of the mouse synaptonemal complex, mouse SCP1, also identified the SC in human primary spermatocytes. Biopsies from 18 men presented with infertility were evaluated by light-field microscopy and grouped into five categories: normal spermatogenesis, Sertoli cell-only syndrome, meiotic disturbances, spermiogenic (i.e. differentiation) disturbances, and other combined disturbances. In all the normal subjects the SCP1 antibody distinctly stained the synaptonemal complexes of primary spermatocytes, whereas Sertoli cells, spermatogonia or spermatids were never stained. In three of the groups, which had germ cells but showed spermatogenic disturbances, the staining was similar to that seen in normal subjects. In sharp contrast to this, in sections from men with Sertoli cell-only syndrome no specific staining was seen. This study demonstrates that a SCP1-related protein is also conserved in the synaptonemal complex in meiotic cells from man. Further studies will reveal to what extent the absence or the non-functionality of SCP1 contributes to male infertility.      

A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a Finnish national birth cohort

As a prerequisite to the use of the Finnish National Hospital Discharge Register in psychiatric epidemiological research, we studied the diagnostic reliability of the register in terms of the psychiatric morbidity experienced by a national birth cohort. We investigated all entries to the register for a sample based upon the Northern Finland 1966 birth cohort at the age of 16 years (n=11017). Until the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis indicating a psychiatric illness, 37 of them being schizophrenia. When operational criteria (DSM-III-R) were applied to clinical information in the available original hospital records for cases of psychosis, personality disorder and substance abuse (n=249), 71 fulfilled criteria for schizophrenia, including all of the 37 cases in the register and an additional 34 (48% false-negatives), most frequently diagnosed in the register as schizophreniform or other psychosis. Despite the official use of DSM-III-R nomenclature, it appears that the clinical concept of schizophrenia in Finland, manifest within the register, remains very restrictive. The application of operational criteria is a necessary prerequisite for scientific research on schizophrenia.     

Rare diseases mimicking acute vertebrobasilar artery thrombosis

Acute ischaemia of the vertebrobasilar circulation leads to a variety of clinical manifestation and is mostly due to cardiogenic or artery-to-artery embolism. We describe four neurological emergency situations involving vertebrobasilar artery aclusion of other origins: basilar migraine, extrinsic compression by rheumatoid inflammatory tissue, generalized vasculitis in subacute rheumatic fever and basilar artery dissection. The differential diagnosis of acute vertebrobasilar artery occlusion may have an important impact on patient management.     

Adjunctive therapy with bromocriptine in Parkinson's disease

Patients with moderately severe Parkinson's disease complicated by the adverse effects of chronic levodopa use benefited from the addition of bromocriptine (Parlodel; Sandoz) in doses up to 26 mg daily, which allowed an approximate 30% reduction of levodopa dose. This resulted in a significant decrease in the amount of levodopa side-effects while maintaining or improving the original parkinsonian clinical stage. Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily. When the doses of bromocriptine were increased slowly, the adverse reactions were minor and usually transient.     

The ileal neobladder: experience and results of more than 100 consecutive cases

The ileal neobladder produces a completely detubularized, low pressure, high capacity reservoir constructed from ileum without any valves. From April 1986 through May 1989, 113 patients underwent this procedure at our institution. Of these patients 99 underwent simultaneous radical cystectomy for bladder cancer and 14 underwent bladder augmentation. The mean postoperative followup was 14.4 months, with a range of 1 to 36 months. There was no perioperative mortality. However, 7 patients died more than 2 months postoperatively: 5 of tumor progression, 1 of pneumonia and severe metabolic acidosis, and 1 of septicemia of unknown cause. Reoperation was necessary in only 13 patients; 10 patients required urethrotomy or dilation of urethral strictures. Day and night continence was preserved in 82.1% of all patients. Stress incontinence, which must be corrected by an artificial sphincter, was found in 4 patients (4.2%) and night-time incontinence that required an external device occurred in 5 (5.3%). Eight patients (8.4%) with mild stress incontinence required no further treatment. Pressure waves exceeding 22 cm. water seldom occurred and then only at maximum capacity. Our experience with this relatively simple system without a nipple is an overwhelming success. The need for reoperation is extraordinarily low and the high reservoir capacity results in continence from the beginning in most patients. The concept is sound and offers a genuine alternative to any form of cutaneous urinary diversion with an incidence of complications not higher than after standard supravesical urinary diversion.     

The correction of postburn deformation of the neck using a musculocutaneous flap from the major pectoral muscle

In 15 patients with the postburn neck deformation, the plasty with a musculocutaneous flap of the musculus pectoralis major was employed. Use of the technique permits to avoid prolonged immobilization of a neck. A good functional and cosmetic result has been noted.     

Ultrasonic diagnosis of meniscus lesions

Controversy exists about the value of ultrasonography of meniscal tears. We therefore examined 101 knee joints of 99 patients in a prospective study. Prior to the arthroscopy the menisci were scanned from an independent team by using 7.5 and 10.0 MHz ultrasound waves. 81 meniscal tears were seen at arthroscopy; 36% of these tears could not be detected with the scanner (? false negative results) while 20% of intact menisci showed positive echogenic structures, which were analysed as meniscal tears. It seems that ultrasonography of the menisci is still of experimental use without any clinical importance.