Clinical implications of the pharmacology of serotonin reuptake inhibitors.

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action. In addition to inhibiting the reuptake of serotonin, TCAs inhibit the uptake of noradrenaline, dopamine and tyramine, and antagonize cholinergic (muscarinic), adrenergic and histaminergic receptors. Moreover, TCAs have quinidine-like anti-arrhythmic activity and lower the seizure threshold. Clinical investigations have shown that the SSRIs have equivalent therapeutic efficacy compared with the TCAs in the treatment of depression. However, the pharmacological specificity of the SSRIs is a clinical advantage since they lack the propensity to cause dry mouth, blurred vision, urinary hesitancy, constipation, hypotension and arrhythmia. Furthermore, the SSRIs are relatively safe in overdosage. The similarities between the SSRIs are more obvious than their differences: all are highly potent and selective inhibitors of serotonin reuptake with efficacy in the treatment of depression. Nevertheless, each has a distinctive pharmacological profile. In this review the characteristics desired in an "ideal" antidepressant are examined, and the ways in which the TCAs and SSRIs fit this ideal are compared.


The acute and long-term treatment of major depression.

Millions of depressed patients do not receive appropriate treatment in spite of the substantial increase in our knowledge about this major medical problem. In addition to individual suffering, there are tens of thousands of deaths by suicide, an increase in morbidity and mortality from medical illnesses whose course is aggravated by an associated depression, a disruptive effect on family life and childrearing, and an economic loss of billions of dollars. Among the many reasons for the inadequate treatment of depression is the fact that the side effects (anticholinergic, antihistaminic, etc.) of traditional antidepressants result in many patients receiving inadequate doses of medication or discontinuing treatment prematurely. The availability of a new class of antidepressant medications--the selective serotonin reuptake inhibitors (SSRIs)--heralds a new phase in the treatment of depression. Although these drugs are not free of side effects, an increased number of depressed patients now seem able to receive adequate doses of medication and to stay on treatment much longer than in the past. The increased acceptance of SSRIs by patients represents an important phase in our ability to effectively treat larger numbers of patients and to prevent relapse in many of them.


Bridging the gap between psychiatric practice and primary care.

The recognition and treatment of psychiatric illness in general practice is a skilled and difficult task and it is estimated that about 30% of psychiatric diagnoses may be missed. Patients whose illness is recognized are more likely to recover at follow-up than those whose illness is missed, demonstrating the importance of adequate training in recognizing psychiatric illness. Many general practitioners find difficulty in using tricyclic antidepressants to treat depression. The usual dose is lower than research evidence accepts as therapeutic and side effects often result in patient refusal to take a full dose. Additionally, the tricyclics are highly toxic in overdose. Many general practitioners in the UK are wary of new treatments because of previous experience of rare side effects leading to withdrawal of some new drugs. However, prescriptions of the selective serotonin reuptake inhibitors (SSRIs) for depression are gradually increasing here and in other countries such as the USA, France and Canada, where the SSRIs as a class account for upwards of 30% of new antidepressant prescriptions. The SSRIs are well suited to general practice; they have a greater therapeutic index than tricyclics, are much safer in overdosage, and have a different range of side effects (mainly nausea) which are better tolerated by patients at therapeutic doses. Furthermore, the SSRIs generally do not require dosage escalation for most patients and evidence indicates that they are effective in the treatment of depression associated with anxiety and insomnia. The safety and efficacy of the new SSRI sertraline has been established in comparative trials versus amitriptyline, imipramine and dothiepin (Reimherr et al., 1990; Cohn et al., 1990; Fontaine, 1991; Langdon, 1991).(ABSTRACT TRUNCATED AT 250 WORDS)


Sertraline in the treatment of obsessive compulsive disorder: two double-blind, placebo-controlled studies.

Sertraline is a non-tricyclic, potent and selective serotonin reuptake inhibitor (SSRI) which is currently approved for the treatment of depression in several countries, including the UK and the USA. The role of serotonin in the aetiology of obsessive compulsive disorder (OCD) has been established through considerable indirect evidence. The strongest evidence comes from the fact that drugs known to be SSRIs have been found to be useful in the pharmacotherapy of OCD. Two double-blind, placebo-controlled studies, including a total of 412 patients, were undertaken to evaluate the efficacy and safety of sertraline in OCD. The first of these studies of a flexible dosing design showed that sertraline, given for eight weeks in daily dosages of 50-200 mg, was a safe and effective treatment for OCD, and superior to placebo. The second study of a fixed dose design and 12 weeks duration confirmed the efficacy and safety of sertraline in OCD at fixed dosages of 50, 100, or 200 mg/day and demonstrated that further improvement in OCD symptoms can be achieved through continued treatment with sertraline. A comparison between the results of these two studies and similar studies with clomipramine shows that, while both drugs have significant therapeutic efficacy, their side-effect profiles may be markedly distinct.


Serotonin and psychiatric disorders.

One of the ongoing problems in biological psychiatry lies in relating clinical laboratory findings to specific symptoms or behaviour patterns. In recent years it has become clear that serotonin (5-HT) is involved in a wide range of psychiatric disorders and in quite specific behaviour patterns, mainly characterized by a poor control of impulses. Psychopharmacotherapy with substances able to enhance the metabolism of serotonin (mainly antidepressants) is able to clinically improve what appear to be very dissimilar conditions. Moreover, antidepressants with serotonergic activity are the only class of drugs able to relieve the symptoms of obsessive compulsive disorder (OCD), which are characterized by a high control of impulses or, more precisely, by a dysfunctional, non-adaptive control of impulses. Recent neurochemical data suggest that a hypersensitivity to 5-HT exists in this condition. Therefore, the hypothesis that serotonin is important for efficient control of impulses is a key to the interpretation of many laboratory findings and to the penetration of the complex field of biological substrates of psychopathology.


[Single-stage urethroplasty using a mobile pedicled cutaneous flap. Value of the extension patch and the tubular flap].

The author presents a well experimented technique for male urethral strictures. This plasty uses a mobile skin flap, taken from the scrotum or the penis, and vascularized from the dartos. The technique performed under locoregional anesthesia, offers a choice of two methods of repair: the widening patch and the substitution plasty, a tubularized graft for urethral substitution. Our technique is applicable to all types of stenoses, allowing one stage repair of all urethral strictures, whatever the cause, the site or the length of the stricture. Attention is called for on two technical points: the size of the flap which must be shorter than the urethral tissue loss; careful dissection of the pedicle, whose excellent blood supply, flexibility and mobility will provide a wide maneuverability to the graft. We have performed 237 cases using this technique and have obtained excellent results (96.7) success rate, which have proven long lasting, as follow-up exceeded 7 years for the oldest cases. Although our technique requires meticulous execution, calling for certain precautionary items that the author attempts to emphasize in this article, this widely used technique, because of its reliability and efficiency, may certainly be considered at first, particularly for the repair of difficult, infected, fistulated, and recurrent urethral strictures.


[Vesicovaginal fistulas. Etiopathogenic and therapeutic aspects in Senegal].

Obstetrical vesicovaginal fistulas are still very common in third world countries, due to the difficulties of medical care. With this series of 123 cases seen over 6 years, we analyze their epidemiological, pathological and therapeutical aspects. A simplified classification is proposed.


[Composition of urinary calculi defined with precision by infrared spectrophotometry].

In order to reduce the relapse of the disease lithiasis, it is very important to have a very good idea about the growth process of the urinary stone. The greatest concern is the recuperation and the profound analysis of the nucleus and the peripheral layers. The preceding morphological study of the stone fragments in combination with the infrared spectrometry is the only manner to know all about the urinary calculus. Many information is lost if only an overall infrared spectrum of the sample is taken.


[Cutaneous ureterostomy with vascular prosthesis. Preliminary results of a new technique].

Cutaneous ureterostomy represents a simplified and less traumatic alternative for urine diversion. The small diameter ureter is often responsible for stenosis of the stomal end. In order to avoid this complication, we developed a surgical method with application of vascular endoprosthesis to prevent stenosis of the ureter. The method was first applied experimentally, and later on 12 patients. A description of the method and the results for the first 12 patients are given. The lack of complication and the good functional results are encouraging, but a longer follow-up and more patients are needed for final evaluation.


[Cancer of the penis. Epidemiological aspects and therapeutic problems in Senegal].

Penile carcinoma is rare in Senegal representing 0.35% of all cancers and 0.97% of cancers in the male adult. Neonate circumcision widely used in this country seems to prevent this disease. With this series of 11 cases, clinical and therapeutical aspects are reviewed.


[Discovery of an undetected thrombosis of the artery of the graft during kidney transplantation. Value of resolution of the obstruction and high pressure kidney washing].

During the transplantation of a kidney, we have discovered an undetected recent thrombosis of the renal artery of the graft, which was revealed after clamp removal by infarction of the kidney. We performed an immediate arterial desobstruction and a secondary high flow rate washing of the kidney, which allowed properly restoring the vascularity of the graft and successfully grafting it.


[Uretero-arterial fistula. A rare cause of massive hematuria].

Ureteroarterial fistulae is a rare condition, with less than 25 reported cases. We describe such a fistula in a young female patient, after radiation therapy for cancer of the cervix and rectovaginal and vesicovaginal fistulae requiring sigmoidostomy and an ureteroureterostomy after long-lasting ureteral intubation. Angiography demonstrated the fistula and the reflux of contrast medium up to the pyelocalyceal cavities, and allowed establishing the origin of the massive hematuria, which caused the patient's death.


[Resection of a pyelonephritic small kidney by celiosurgery].

The authors report about the exeresis of a pyelonephrictic left small kidney with laparoscopic surgery. First a ureteral tube was inserted to facilitate detection of the ureter by laparoscopy possible after reclining the colon. Dissection of the ureter was taken up to the hilum and pedicle, which was severed between rows of clamps by means of the endoscopic GIA stafler. The operation lasted 4 hours and 30 minutes. The blood loss was minimal and the stay in hospital was of three days.


[Syndrome of the pyelo-ureteral junction of the graft after kidney transplantation. Apropos of 2 cases].

We report 2 cases of decompensation of a pelviureteric obstruction in a transplanted kidney. In one case, the pyeloureteral obstruction was discovered intraoperatively during grafting (cadaver kidney) and was corrected at that time. In the other case, the obstruction was decompensated one month after grafting (kidney taken from a living donor with a very discrete bilateral junction syndrome) and required surgical treatment. The procedure used in both cases was a pyelopyelic anastomosis after nephrectomy of the recipient's kidney.


[Cancer of the urachus].

We report a case of mucin-producing adenocarcinoma of the urachus. Preoperative diagnosis was established by computerized axial tomography. An en bloc resection was performed, including the urachus with supravesical mass and bladder dome.


[Hemorrhagic complications revealing renal angiomyolipoma. Apropos of 2 cases].

Renal angiomyolipomas are rare benign tumors, which are most often discovered with ultrasonography, owing to the hyperechogenicity of their fatty component, and with computed tomography. The authors report about two cases of severe hemorrhagic complications revealing a renal angiomyolipoma, for which computed tomography made a preoperative diagnosis possible.


The evaluation of analgesic effects in cancer patients as exemplified by a double-blind, crossover study of immediate-release versus controlled-release morphine.

We compared the effects of controlled-release and immediate-release morphine preparations in adult patients with moderate-to-severe cancer pain and report methodologic approaches to pain evaluation. The study consisted of a two-phase randomized crossover trial preceded by a titration phase; all phases were conducted under double-blind conditions. To evaluate pain intensity, a visual analogue scale (VAS) and the Present Pain Intensity scale of the McGill Pain Questionnaire were used. Additional morphine solution for breakthrough pain was used as an outcome measure. Pain was evaluated nine times daily, which permitted correlation of pain scores with the pharmacokinetic patterns of the test drugs. Side effects were rated once daily, using a scale from 0 to 3. To assess the relative importance of side effects, a toxicity index was designed based on both the intensity and duration of each side effect. The overall VAS pain scores during treatment with controlled-release and immediate-release morphine were 1.3 (SD = 0.1) and 1.4 (SD = 0.2), respectively. Use of supplemental morphine solution for breakthrough pain expressed as the percentage of the daily dose of the test drug was 5.5% for the controlled-release drug and 10.9% for the immediate-release drug. Differences in pain scores, side effects, and supplemental morphine requirement between the two groups were not significant. We discuss methodologic issues in double-blind clinical trials of analgesics, in particular the validity of "Patient Preference" as an outcome measure and problems related to the titration phase.


A comparative study of controlled-release morphine (CRM) suspension and CRM tablets in chronic cancer pain.

This study compared the efficacy and the adverse effects of controlled-release morphine (CRM) suspension (SAR 213) and CRM tablets (Moscontin) in the treatment of cancer pain. This multicenter, randomized, double-blind, double-dummy, crossover study was carried out on 52 patients. Each patient received both study treatments given at an equivalent dosage of morphine during each of two 7-day periods. The primary outcome variable was the severity of pain assessed three times daily by means of a visual analogue scale. Secondary criteria of efficacy were the severity of pain assessed by verbal rating scale, the need for "rescue" doses of immediate-release morphine, treatment preference, and indices of quality of life (activity, mood, sleep). There were no statistically significant differences in the parameters assessed when comparing the two groups. This study shows that, when prescribed at the same doses, CRM suspension and CRM tablets have similar efficacy and adverse effects, as well as the same duration of action. The results of this first clinical study carried out on CRM suspension are especially relevant for patients with cancer pain who have difficulty swallowing.


Pharmacokinetics of two novel rectal controlled-release morphine formulations.

Administration of morphine by the oral route is not possible in cancer patients who are unable to swallow or are intolerant of oral morphine. Thus, there is a need for reliable alternate routes of drug administration. We compared the bioavailability of two prototype 30-mg morphine sulfate controlled-release suppository formulations (high and low viscosity) with 30-mg oral controlled-release morphine sulfate tablets in a 14-subject single-dose randomized, three-way crossover study. Venous blood samples were obtained immediately prior to and for 24 hr following each dose. Morphine concentrations were determined by radioimmunoassay. Compared with oral controlled-release morphine, the high- and low-viscosity suppository formulations had significantly greater bioavailability (AUC0-24 72.7 +/- 13.2 for the oral preparation versus 98.6 +/- 35.7 and 105.8 +/- 37.3 ng.hr/mL for the suppositories, respectively, P < 0.05), later peak concentration (tmax 2.3 +/- 0.8 versus 3.1 +/- 2.3 and 5.0 +/- 1.5 hr, respectively, P < 0.05), and longer half-value duration (4.3 +/- 1.6 versus 10.4 +/- 5.5 and 9.5 +/- 4.3 hr, respectively, P < 0.05). Peak concentration for the high-viscosity suppository formulation (Cmax 7.75 +/- 2.66 ng/mL) was significantly lower than the low-viscosity suppository (Cmax 9.23 +/- 2.85 ng/mL) and the oral tablet (Cmax 10.4 +/- 2.78 ng/mL) formulations (P < 0.05). The increased bioavailability observed with the two controlled-release suppositories may be the result of partial avoidance of hepatic biotransformation with rectal administration.


Hospital palliative care services: three models in three countries.

There is an increasing trend toward providing palliative care services within general hospitals. The history and work of three hospital palliative care teams is reviewed, one in New York, one in London, and one in Ontario, Canada. The evolution, leadership, structure, functioning, and financing of the teams is discussed. Indicators of success and survival, principally financial support, leadership, and acceptability within hospitals, are considered. It is recommended that the service traditionally limited to oncology patients be extended to other patient groups. It is also recommended that, taking into account cultural and institutional differences, standardized mechanisms be adopted so that services can be systematically audited and changes implemented. Research and education will become increasingly important if services within hospitals are to survive.


Home palliative care: results in 1991 versus 1988.

Home care is greatly expanding because of the savings it offers by avoiding unnecessary hospitalization and also because patients benefit from being in their own home environments. Since 1988, Societa Assistenza Malato Oncologico Terminale (SAMOT) has organized a pain relief and home palliative care unit for terminal cancer patients. Objectives, difficulties, protocols, and achievements of 4 years of experience were examined, and the findings of the various years were compared. Our results suggest that considerable progress has been made in home palliative care. There are still social and cultural difficulties to overcome, however.


Fentanyl: clinical use as postoperative analgesic--epidural/intrathecal route.

The administration of epidural and intrathecal opioids for the management of postoperative pain is well established. Fentanyl, because of its greater lipophilicity, offers a number of advantages over morphine for epidural analgesia, including a lower incidence of side effects and reduced risk of delayed-onset respiratory depression. The relatively short duration of action of epidural fentanyl makes this agent more ideally suited for continuous infusion or patient-controlled epidural analgesia (PCEA). The effective doses and adverse effects profile of epidural fentanyl are reasonably well understood. Because of the lack of spread through the cerebrospinal fluid (CSF) and hence the segmental nature of the analgesia achieved, location of epidural catheter placement is of paramount importance when this agent is used. Prolonged epidural infusion of fentanyl may result in high systemic concentrations not dissimilar to IV infusion, and, therefore, the greatest efficacy of epidural fentanyl administration may be in combination with low concentrations of bupivacaine, an approach that achieves a synergistic effect. 2-Chloroprocaine has been shown to antagonize epidural fentanyl analgesia. Intrathecal fentanyl for postoperative analgesia is limited by its short duration of action with single-bolus administration. The widespread international increase in the use of epidural fentanyl for postoperative analgesia promises further improvements and refinement in techniques.


Long-term stability after inferior maxillary repositioning by miniplate fixation.

Nineteen patients underwent Le Fort I osteotomy and inferior maxillary repositioning. Miniplates were used to maintain the maxilla in its new position. The patients were followed from 12 to 58 months, postoperatively. Fourteen patients were considered to be stable over the long term. Five patients had a long-term relapse of more than 30%. A tendency towards greater relapse was seen in patients with more than 5 mm inferior repositioning, and in patients who had concurrent segmental osteotomies of the maxilla. In spite of the use of miniplates, there continues to be an element of unpredictability with regard to vertical relapse after inferior maxillary repositioning, and this may be related to soft-tissue influences.


The sagittal ramus osteotomy. Stability of fixation with internal miniplates.

Radiographs of 15 patients who underwent sagittal split mandibular ramus osteotomy with rigid miniplate fixation for mandibular lengthening were studied. Evaluation of postoperative stability of the mandibular lengthening at 6 months to 2 years revealed minimal postoperative changes.


Two similar "bad splits" and how they were treated. Report of two cases.

Two high fractures of the proximal segments during separate sagittal split osteotomies were treated by a modification of the "Obwegeser II" technique and screw osteosynthesis. Careful wedging of the large spreading osteotome in a more superior position while splitting up to the posterior border will probably prevent such complications.


Unusual nasoendotracheal tube damage during Le Fort I osteotomy. Case report.

An unusual case of endotracheal tube damage during Le Fort I osteotomy is presented. A minor change in design of the tube might prevent similar complications.


Maxillofacial fractures in a Norwegian district.

Records of 169 patients referred to Haukeland Hospital, Bergen, Norway, for treatment of maxillofacial fractures during the period 1989-91 were studied with respect to socio-etiologic aspects, frequency and localization of jaw fractures, treatment, and complications. The number of maxillofacial fractures found in the present study was about twice as many as found in a study from the same area during the period 1974-9. Recent trends in the etiology of maxillofacial traumas were confirmed, such as increased number of fractures caused by interpersonal violence, and a reduction of cases related to traffic accidents. Alcohol abuse was a contributing factor in 28% of the patients. Mandibular fractures were 4.8 times more frequent than maxillary fractures. Reduction and fixation with miniplate osteosynthesis was the preferred treatment in most patients.


Screwdriver aspiration. A complication of dental implant placement.

Endosseous implants are part of the prosthodontic rehabilitation of patients who have undergone radical tumor resection in the oral and maxillofacial area. Several complications arising from the use of these implants have been reported. Intraoperative aspiration of a screwdriver as a rare and life-threatening complication is presented. It was followed by a chain of further complications including pneumothorax, late laryngeal obstruction requiring tracheotomy, and pleural effusion requiring drainage. To prevent similar complications, we recommend general anesthesia when placing dental implants in patients who have previously undergone extended radical tumor surgery of the oral cavity.


A new method of reconstruction in a patient undergoing bilateral total maxillectomy.

A new application of the titanium hollow screw reconstruction plate (THORP) system, originally designed for bridging mandibular defects, is presented. Because of the screw-plate locking principle, the system allows rigid fixation of the plate without unphysiologic load to the bone underneath. A case is presented with a large squamous cell carcinoma requiring bilateral total maxillectomy. The titanium plate was attached horizontally to the zygomatic bones with two titanium hollow screws on each side. Six months later a prosthetic device was constructed and attached to the exposed part of the plate by a modified bar and clips system. The patient is able to speak, chew, and swallow without difficulty.


Acinic cell carcinoma of the maxillary sinus. A case report.

A case of acinic cell carcinoma of the maxillary sinus is presented. As can be assumed from the number of reported cases, this is an uncommon site for this tumor to occur.


The desmo- and osteoplastic ameloblastoma. Histologic variant or clinicopathologic entity? Case reports.

Two cases of desmoplastic ameloblastoma (DA) are presented, bringing the total number of reported cases to 29. One case of the so-called "hybrid lesion" is added to the presentation. Immunohistochemical studies indicate that the desmoplasia is caused by active de novo synthesis of extracellular matrix proteins. Moreover, the DA may also show osteoplasia, and this probably explains the characteristic radiographic appearance of many DAs, i.e. the occurrence of both radiolucent and radiopaque changes, suggestive of a fibro-osseous lesion. Many more cases of DA are needed to clarify the true nature of this most interesting tumor.


Clear-cell ameloblastoma of the mandible (a case report).

An ameloblastoma with histologic evidence of clear cells in a 15-year-old Nigerian male patient, who presented with a slow-growing, intraosseous, anterior mandibular swelling, is reported. The lesion was treated by surgery alone, and has not shown any recurrence 5 years after initial surgery.


Sonography of nonneoplastic disorders of the salivary glands.

We examined 637 patients with salivary gland disorders by real-time sonography. In 270 patients, the possibility of neoplasia of the salivary glands could not be excluded by ultrasound. In the remaining 367 patients, the following disorders were diagnosed sonographically: acute inflammation (72 patients), Sjögren's syndrome or chronic inflammation (81 patients), abscess (9 patients), sialolithiasis (192 patients), and cysts (13 patients). The present study discusses the ultrasound appearances of a variety of diseases and the indications and limits of sonography in the evaluation of salivary gland pathology.


Sialographic changes related to clinical and pathologic findings in chronic obstructive parotitis.

This paper presents the results from a study of 23 patients with chronic obstructive parotitis (COP) in whom the sialographic changes were related to the clinical and histopathologic features. The sialographic changes were divided into four types. The stimulated parotid flow rate (SPFR) was normal in sialography Type I patients, while SPFR was significantly reduced in Types II, III, and IV patients, as compared with healthy persons. The changes observed by light microscopy were irregular dilation and chronic inflammation of main and branching ducts with saliva deposits in the enlarged luminal system. Ultrastructural changes included degeneration of ductal epithelial cells, marked proliferation of periductal fibrous tissue, and moderately electron-dense deposits in the lumen of the dilated peripheral ducts. The extent of the histopathologic changes largely paralleled the severity of the sialographic changes. These findings indicate that COP is a relatively common inflammatory disease and that the sialographic classification reflects the severity of the disease.


Computer-aided optimization of choice and positioning of bone plates and screws used for internal fixation of mandibular fractures.

The present study describes a biomechanical integrated model of the mandibular system in which the maxilla and mandible, the masticatory muscles, and the temporomandibular joints are regarded as one system. In this model, strains in plate-osteosynthesis devices for internal fixation of mandibular fractures can be minimized by optimizing their positions. The model evaluates maximal bite force strategies on all possible dental elements; it uses a linear programming technique and a muscle architecture model, resulting in muscle recruitment patterns. The shape of a "standard" lower jaw is digitized by means of a three-dimensional (3-D) coordinate retrieval device and drawn on a computer screen after its dimensions have been changed according to the clinical case at hand. The 3-D location of the fracture as well as the anatomic restrictions for screw placement can be indicated on the screen. Osteosynthesis devices can be indicated in terms of dimensions, number, and material properties.


[Laparoscopy-guided extraperitoneal resection of ovarian cysts: surgical procedure, indications and limitations].

We designed a new surgical method for the treatment of benign ovarian cysts. We have previously reported that, with our laparoscopy-guided method, the cyst wall is pulled outside the abdominal cavity after evacuation of the cyst contents, and resection is performed by the same method as during laparotomy. The preoperative assessment and surgical findings were investigated in 16 subjects, 5 with simple cysts, 2 with para-ovarian cysts, 2 with chocolate cysts, 5 with dermoid cysts and 2 with mucinous cysts. This surgical method was applicable in 11 of the 14 patients. Laparotomy was required in the other 3, because 2 of the patients had strong adhesions and in 1 evacuation was impossible. The patients were classified into 3 grades of difficulty before surgery: Grade I; operable, Grade II; operable with special care, Grade III; laparotomy required. During surgery, the feasibility of continuing the procedure was also assessed. In this surgical procedure, through a small incision in the abdominal wall, the entire resection of an ovarian cyst is done extra-peritoneally. However, the eligibility of patients for this method needs to be very carefully examined preoperatively and reviewed throughout the procedure.


[Fetal hemodynamics assessed by transvaginal color flow mapping during the first and early second trimesters].

The present study has been carried out to evaluate the usefulness of transvaginal color flow mapping in the assessment of fetal hemodynamics during the first and early second trimesters. Forty normal fetuses were examined by transvaginal color flow mapping from 12 to 20 weeks of gestation. Maximum velocity in the transmitral (MVmax), transtricuspid (TVmax), transaortic (AVmax), fetal descending aorta (Vmax) and fetal internal carotid artery (ICVmax) was assessed. The systolic/diastolic ratio and pulsatility index (PI) of umbilical artery was also assessed. The detection rates for the fetal and umbilical flow velocity waveforms were 42.5%-85.0%. In particular, intracardiac blood flow velocity was easy to detect by transvaginal color flow mapping. The Vmax, ICVmax, MVmax, TVmax and AVmax increased significantly with advancing gestation in the normal fetuses. The TVmax was lower than the MVmax during the first and early second trimesters. Transvaginal color flow mapping studies can improve the understanding of the characteristics of fetal blood flow during the first and second early trimesters. Thus it seems to be useful in making an accurate antenatal diagnosis of congenital heart disease earlier.


[Development of method for measurement of pulsatile change in arterial diameter in the fetus].

The present study was designed to evaluate perfusion dynamics of organs by measuring pulsatile change in arterial diameter concomitant with flow velocity determination. An ultrasonic phased locked echo tracking system equipped with a real time linear array scanner was used to measure pulsatile change in arterial diameter. The distance from the transducer to a distal or proximal point on the inner vessel wall can be defined as the relative time difference of the zero cross for each reflective wave. The pulsatile change in the arterial diameter was a reflection of intra-arterial pressure change which was confirmed by simultaneous measurement of direct pressure in the adult brachial, femoral and descending aorta (DA) by arterial catheterization. The accuracy of measurement of arterial diameter and pulsatile change were confirmed by the coefficient of variation (C.V) in the diameter of than 4% in the former and less than 8% in the later in both inter- and intra-assay variance. In normal growth fetuses, the pulsatile changes in the DA were within the range of about 10% of the minimum arterial diameter. Intrauterine growth retarded fetuses (IUGR) who had a high pulsatility index (PI) were 7.26 +/- 0.36% (n = 5, p < 0.01 v.s. normal growth group) and showed discrete figures between pulsatile and blood flow velocity waveforms. Furthermore, large for date fetuses (LFD) who had a high PI were 12.20 +/- 0.50% (n = 3, p < 0.05 v.s. normal growth group) and had similar figures in pulsatile and blood flow velocity waveforms.(ABSTRACT TRUNCATED AT 250 WORDS)


[Multimodal treatment for advanced, ovarian cancer patients with poor performance status--its effectiveness and limitations].

We assessed the feasibility of the sequential multimodal treatment including neoadjuvant chemotherapy for far advanced ovarian cancer patients not amenable to a standard modality because of poor medical status. Seven consecutive advanced ovarian cancer patients presented with massive ascites (5 with pleural effusion). Based on the priming theory, immunotherapy with OK432 (s.c. priming with 0.2 KE of OK432 followed by a local injection with 10KE of OK432) was successfully applied to a carcinomatous effusion. Thereafter, patients were treated with 4-6 courses (13-20 wks) of "low-dose consecutive CP (CPM 500 mg/m2, day 1; CDDP 10 mg/m2, day 1-7), which delivered 1CR, 5PR and 1NC (tumor regression rate: 30-100%). Subsequently, the patients underwent radical surgery including small/large bowel resection, splenectomy and diaphragma resection in addition to hysterectomy, bilateral adenectomy and omentectomy, with tumor resectability being 100% in 4 cases and 90% < (residual 2 cm) in 3. Postoperatively, patients received intraperitoneal (IP) chemo-immunotherapy and were followed up with IP washing cytology through an implanted reservoir. Mean survival time was 17.1 months (10-32) with the follow up interval being 10-32 months. Four patients with complete tumor resection are alive with no evidence of disease for 14-32 months. Among 3 incomplete patients, 2 with persistent/recurrent disease received further IP chemotherapy and the remaining one died of the disease at 15 months from the start of therapy. Thus, the present multimodality indicates the possibility of a "cure" for far advanced ovarian cancer patients with poor performance status.


[Comparison of the indirect immunobead test and the sperm immobilization test for detection of antisperm antibody].

The indirect immunobead test (indirect IBT; IgG.IgA) and the sperm immobilization test (SIT) were carried out for 75 infertile patients to detect antisperm antibodies in the sera. The results were as follows. 1) Twenty three cases showed positive results in the IBT, and 14 out of the 23 showed also positive in the SIT. 2) Fifty two cases which had negative results in IBT also had negative results in SIT. 3) IgG-IB attached to sperm were observed in 14 with positive SIT, but no IgA-IB were observed in 4 cases out of the 14. 4) IgG-IB attached to both the sperm head and end-tail in 12 cases out of the 14, but only to the sperm end-tail in the other 2 cases. We therefore concluded that, 1) IBT detected anti-sperm antibodies more readily than SIT. 2) IBT was an alternative to SIT for screening. 3) Sperm immobilization antibodies appeared to be in the IgG class rather than in the IgA class. 4) It appeared that sperm immobilization antibodies might be able to attach to the sperm tail as well as the head.


[The role of fibronectin in repairing fetal membrane].

The fibrin adhesion technique is being recognized as a way to prevent amniotic fluid leakage in the case of preterm premature rupture of the fetal membrane (PROM). However, the effect of fibrin adhesion is still not clear. The aim of this study is to investigate the implications of fibronectin in repairing the fetal membrane. We divided 9 normal fetal membranes into 4 groups. In all the groups, an incision was made in the membrane with a sterile knife. Group A: The incisions in the membranes were sealed with fibrinogen and thrombin (N = 9). Group B: The incisions in the membranes were sealed with fibrinogen and thrombin with fibronectin (N = 9). Group C: Fibronectin was added to the culture medium containing fetal membranes (N = 9). Group D: The fetal membranes were cultured in the medium alone (N = 9). All membranes were cultured for 6 days in 10% fcs added to MEM and analyzed histologically. In group A, fibrin clots did not attach to the membranes at all. In group B, fibrin clots attached closely to the membranes. In group C, fibroblasts increased remarkably at the incision sites on the fetal membranes. In group D, fibronectin accumulated at the incision sites on the fetal membranes. These results suggest that fibronectin is important in repairing fetal membrane.


Utilizing the nursing process in the ophthalmic operating room documentation.

Nursing documentation has always been regarded not only as time consuming but a nursing activity that is problematic when it comes to compliance. Somehow nurses must find the balance between documentation of significant events and observations versus duplication or repetition of routine patient activities. This paper describes how these problems were met by one institution.


Carotid fistula.

Frequently it is the ophthalmic nurse who obtains the patient's pertinent health history and background information. This case study of a patient diagnosed with an orbital carotid fistula shows how the nursing history helped to solve the patient's diagnosis.


Eyeglasses and common complaints.

About one-half of the population wear eyeglasses. For them, a pair of eyeglasses is a necessary aid and when properly fit, can provide clear and comfortable vision for a variety of daily activities.


Ophthalmic nursing assessment.

This article is written to assist the ophthalmic nurse in performing a basic assessment of the eye and provide a system for easy documentation. Many nursing physical assessment forms are developed to collect and organize data. However, there is very little published in gathering pertinent data on the ophthalmic patient in either the outpatient or inpatient setting.


[Cap brace: a new treatment for newborn and infant congenital muscular torticollis].

Herein is reported a new treatment, using a cap brace, for congenital muscular torticollis (CMT) in newborn and infant. The subjects consisted of 72 cases undergoing cap brace treatment (CB-group), and 197 cases undergoing ordinary treatment (O-group) for CMT. In children of the O-group, the rolling-over developmental stage was later than in normal infants, while in those of the CB-group this stage was not delayed. The good prognostic factors for lessening cranial and facial asymmetry, evaluated by chi-square test, were as follows: partus praematurus, a high APGAR score, breast-feeding, an early start to rolling-over, early vanishing of the sternomastoid tumor, and early vanishing of limitation of neck movement. For discriminant analysis of the factors related to cranial and facial asymmetry, the quantification method of the second type was used. In the O-group, discrimination between asymmetry and no asymmetry was achieved (R = 0.832), but in the CB-group the factors involved could not be discriminated. Moreover, ultratomosonography was very useful for examining the sternomastoid muscle. The internal echogenicity changed from low to high with aging, and was the echo pattern was classified as types I to IV accordingly. Patients with an early change from type I to type II tended to show good results in cranial and facial asymmetry. This brace was developed with an improvement of the other similar braces. But unlike other devices our brace did not fix the infant's head in one position for correction. And as a result of this virtue, the sternomastoid muscle of the affected side was relaxed and the vanishing periods of asymmetrical tonic neck reflex are hastened. Use of this brace improved the cure rate and was especially effective in decreasing cranial and facial asymmetry.


Effects of enforced exercise on biomechanical properties of the anterior cruciate ligament of bipedal rats.

The purpose of this study was to evaluate the effect of enforced exercise on the biomechanical properties of the anterior cruciate ligament (ACL) in bipedal rats. These rats were divided into two groups: (1) bipedal rats without exercise, E(-)G, and (2) bipedal rats with exercise for 4 weeks, E(+)G. Strength (the maximum load that can be sustained by specimen prior to rupture) results for E(+)G were significantly lower than those for E(-)G at the loading rates of 8.3 mm/sec and 1 x 10(3) mm/sec. Stiffness (the slope of the load-deformation curve for a specimen with a linear-deformation relationship) results for E(+)G were significantly lower than those for E(-)G at the rate of 8.3 mm/sec. A load relaxation test (a test of viscoelastic behavior characterized by a decrease of load in a specimen with time under a constant load or deformation) showed a larger load-relaxation phenomenon (a decline in load over time under a constant deformation) in E(-)G. Analyzing these results by a three-element model, we found that the viscosity was higher in E(+)G than in E(-)G. This study offers insight into the effects of exercise on the ACL of humans.


[Development of synthetic bone models for the evaluation of fracture fixation devices].

Mechanical tests are indispensable for the research and development of internal devices used for fracture fixation. It is ideal to use fresh human bones even for in vitro experiments. However, fresh human bones are difficult to access, so that alternative materials have been developed. In this study, the applicability of synthetic tibia or femur models made from polyurethane resin (Hiprox) was studied, comparing the mechanical properties of both the synthetic models and the fresh human bones under fracture-fixation conditions using various fixation devices. When the models were designed to simulate the cortical bone with solid resin and the cancellous bone with porous resin, the mechanical properties can be fairly approximated to those of the fresh human bones. It was concluded that the Hiprox models are useful in for preliminary testing of fracture fixation devices.


[Experimental study on the effect of forced running on occurrence of osteoarthritis in the knee of C 57 BL mice].

We investigated the effects of running load on the development of osteoarthritis (OA) in C 57 black male mice (Silberberg), a strain which spontaneously develops OA of the knee joint, and in Std:ddy male mice, a strain which does not develop OA. Six-week-old mice of both strains were randomly assigned to a non-forced running (control) group or forced running groups, which ran on treadmill 1 or 2 hours per day of 5 day/week program. Six, 18, and 30 weeks after the running period, the mice were sacrificed and the knee joints examined histologically and bone morphometrically. In the control C 57 black mice, OA occurred at 6 months of age, while in the forced running C 57 black mice, OA occurred at 3 months of age (6 weeks after the end forced running). In 6 and 9 months old C 57 black mice the incidence of OA in the forced running group was higher than that in corresponding control group. These data suggest that forced running load accelerates the process of OA in the knee joint in young mice of a strain which spontaneously develops OA.


[Mechanism of adhesion of polyphenolic protein and its potential for clinical application].

The protein of the marine mussel Mytilus edulis L. known as "polyphenolic protein (ppp)" evolved specifically to allow mussels to attach strongly to solid surfaces in the sea and plays an important role in anchoring this mollusc to ocean rocks. In the present study, the mechanism of the adhesiveness of ppp in a "wet environment" was investigated. The adsorption of ppp to both glass and polypropylene was very rapid, and it reached saturation within 10 minutes. When the concentration of ppp was low, it formed a monolayer on glass surfaces, and its affinity for the surface proved to be as great as that of poly-D-lysine which is generally considered to have a strong affinity for solid surfaces and is applied as a cell adhesive. On the other hand, when the ppp concentration exceeded 5.0 x 10(-3) mumol/ml, multilayer adsorption to glass was observed. Moreover, when ppp was modified by tyrosinase, intermolecular condensation occurred which was contributed to a rigid adhesion by cross-linking between the dopa and lysine residues of ppp molecules. These findings provide important information on the development of a new type of adhesive for use on living tissues.


[An experimental study on elongation injury of peripheral nerve].

The sciatic nerve of rabbits was indirectly elongated by lengthening the femur to clarify the pathology of elongation injury of the peripheral nerve. Electrophysiologic and morphologic changes and the blood flow in the nerve due to nerve elongation were evaluated in this model. No significant changes were observed when the nerve was elongated by 5.01%. Conduction disturbances, however, developed and the blood flow in the nerve was markedly reduced by sustained 11.8% elongation. In the latter case, the blood-nerve barrier was disrupted after 6-12 hours, endoneurial edema was observed after 48 hours, and extensive degeneration of nerve fibers was noted after 5 days. When the nerve was returned to the original length after 11.8% elongation for 2 hours, degeneration of the nerve fibers followed only partially. These findings suggest that circulatory impairments as well as mechanical damages are closely involved in elongation injury of peripheral nerves. The results also indicate that the duration of elongation plays an important role in determining the severity of elongation injury of peripheral nerves.


Opponensplasty by extensor indicis and flexor digitorum superficialis tendon transfer.

From 1977 to 1988, 166 patients with median nerve paralysis of varied aetiology underwent opponensplasty. In 50 of these the extensor indicis was used, and in 116 the flexor digitorum superficialis of the ring finger. An analysis of these hands showed that the EI opponensplasty was best in supple hands and FDS opponensplasty was more suitable for less pliable hands. There were fewer complications seen after FDS opponensplasty if the detachment of the donor tendon was done through a volar oblique incision rather than the conventional lateral incision.


Restoration of pinch in ulnar nerve palsy by transfer of split extensor digiti minimi and extensor indicis.

Subcutaneous transfer of the ulnar slip of the extensor digiti minimi (EDM) to the adductor tubercle across the dorsum of the hand restores pinch, and index finger abduction is reproduced by re-routing extensor indicis proprius around the thumb extensor tendons. Six patients with post-traumatic ulnar palsy have been treated by this method with a minimum follow-up period of 40 months. Pinch was improved from an average of 5% to 40-50% of the normal side, and index abduction to 30-40%. There was no donor morbidity.


Flexor digitorum superficialis tendon transfer for intrinsic replacement. Long-term results and the effect on donor fingers.

This study is a review of 127 hands in 100 patients in whom one or two FDS tendons were used to correct claw-hand deformity and/or loss of opposition of the thumb. In lumbrical replacement the results were graded as excellent in 16 hands (21%) and good in 43 hands (57%). For opponensplasty the results were excellent in 26 hands (32%) and good in 42 hands (51%). Possible defects that can develop in the donor finger are: swan-neck deformity, flexion posture of the DIP joint, not as part of the swan-neck deformity, check-rein deformity or flexion contracture, and insufficient finger flexion. Of the 158 fingers swan-neck deformity was seen in 15%, DIP flexion in 29%, check-rein deformity in 26% and insufficient finger flexion in 18%. The latter occurred with another defect. In 48 fingers (30%) no defects were observed.


The blood supply of digital nerves: a microanatomical study of superficial and deep palmar venous networks.

In this work on vascularization of digital nerves, we have studied the anatomy of the deep network of venae comitantes of digital arteries, and the system of superficial palmar venules. 22 specimens of nerve and artery were dissected as one unit and were infused with Microfil prior to study under the microscope. The deep venous network, a satellite of the digital artery, can be classified into four types. A true network of deep venae comitantes exists in three of these four types, drained by deep veins arising from the transverse anastomotic arches between the palmar digital pedicles. Vascularization of the digital nerve is supplied by numerous anastomotic vessels connecting epineurial vessels, digital artery and the periarterial network (venae comitantes and vasa vasorum). This anatomical configuration lends itself to vascularized nerve grafting; for example, it is possible to use a nerve/artery graft taken as a unit from an amputated finger unsuitable for replantation. Two types of valves in this superficial venous network have been identified and their function is discussed.


The terminal branch of posterior interosseous nerve: a useful donor for digital nerve grafting.

The anatomical relationships of the terminal branch of posterior interosseous nerve have been studied in 57 cadaver and amputation specimens. Removal of the nerve leaves the patient with no apparent sensory deficit. In all dissections the nerve was present and its location was constant. The mean obtainable length was 3.7 cm (range 2.7-5.1 cm) and its cross-sectional area made the nerve suitable for grafting of digital nerves.


Replantation of the radial side of the hand in the rhesus monkey: anatomical and functional aspects. A preliminary study to composite tissue allografting.

Before human hand transplantation can even be considered, an appropriate research model must be studied in a non-human primate. The first ray of the hand, augmented with a radial forearm flap, was chosen as a functional composite tissue graft. Four technically successful replantation of the radial unit have been carried out. One monkey died on the first post-operative day due to cardiac arrythmia. Normal wound healing occurred in the other three animals. In three monkeys, functional sensory and motor recovery was almost complete. The monkeys were able to pick up small particles of food with the index finger and thumb. It is suggested that this model could be used for allogeneic composite tissue transplantation in a non-human primate.


Arteriovenous fistulae after free flap surgery in a replanted hand.

AV fistulae are extremely rare complications after hand replantation. In the case presented, the formation of an AV fistula did not occur immediately after the replantation, but after the insertion of the free lateral arm flap to the extensor surface of the replanted hand. This paper discusses the mechanisms responsible for the formation of AV fistulae.


Operative findings in camptodactyly of the little finger.

In five of six cases of camptodactyly in which an abnormality of the flexor tendon was examined at operation, the flexor digitorum superficialis tendon was hypoplastic and there was no continuity of the normal tendon between the muscle belly and bony insertion. The proximal end of the flexor digitorum superficialis tendon was attached to the palmar aponeurosis and the flexor tendon sheath of the ring finger in two patients, to the palmar aponeurosis in one, to the undersurface of the transverse carpal ligament in one and to the flexor tendon sheath of the ring finger in one. The tenodesis effect of the abnormal tendon of the flexor digitorum superficialis is considered to play an important role in the cause and rapid increase of the deformity of camptodactyly.


Long-standing extended dynamic splintage and release of an abnormal restraining structure in camptodactyly.

62 patients with camptodactyly of the little finger have been reviewed, and only five cases failed to respond to conservative treatment. These cases are reported. One patient could straighten the deformed PIP joint with snapping, and the other two were resistant to conservative treatment and were found to have a restraining structure requiring release. These findings are in keeping with an imbalance between flexion and extension forces due to long-standing malposition of the extensor lateral bands. Operative treatment should be reversed for cases of failed conservative treatment, which should be started as early as possible.


Acrylic resin finger prosthesis.

A technique is described for the prosthetic replacement of two fingers using acrylic resin. Retention was obtained using finger rings. The stages of the technique are outlined. Advantages and disadvantages are briefly stated.


Mycobacterium fortuitum infections of the hand. Report of five cases.

Five cases are reported of infection due to Mycobacterium fortuitum involving the hand following contaminated injection or traumatic wounds. Synovectomy, debridement, or amputation together with prolonged chemotherapy using kanamycin or amikacin were required. Doxycycline and sulphamethoxasole also seemed to be the effective antibiotics for this organism. A high index of suspicion is important in order to obtain the correct diagnosis.


The gymnast's wrist: acquired positive ulnar variance following chronic epiphyseal injury.

Five cases of symptomatic acquired positive ulnar variance are described. All cases occurred due to premature physeal closure of the growth plate in teenage girl gymnasts. All cases demonstrated ulnocarpal impingement, for which we describe a clinical test. Arthroscopic assessment of the wrist allowed us to assess the integrity of the TFCC (triangular fibrocartilaginous complex) and decide on the most appropriate surgery. Two patients needed distal ulna recession and one needed shaving for a TFCC perforation, with a good result.


The Swanson ulnar head prosthesis for post-traumatic disorders of the distal radio-ulnar joint.

20 Swanson ulnar head prostheses inserted for post-traumatic disorders of the distal radio-ulnar joint were reviewed at a mean of 44.2 months post-operatively (range 12-104 months). The indication for surgery was painful loss of forearm rotation with or without ulno-carpal impingement and ulno-carpal instability. Symptoms in 16 patients were the result of malunion following severe distal radial fractures (two Frykman 7 fractures and 14 Frykman 8 fractures), and in the remainder were due to unreduced dislocations in the distal radio-ulnar joint (two patients) or unsatisfactory Darrach procedures (two patients). 70% of patients achieved excellent or good clinical results despite the fact that radiographs showed bone resorption in all cases, tilting of the prosthesis in 40% and implant fractures in 15%.


Silicone rubber distal ulnar replacement arthroplasty.

We retrospectively reviewed 42 patients who underwent resection of the distal ulna with implantation of a silicone rubber ulnar head prosthesis (45 wrists). Two prostheses were used: the original Swanson prosthesis, and a prosthesis of our own design. Follow-up X-rays showed migration or breakage of 63% of the prostheses. No statistically significant correlation existed between the quality of functional outcome and the integrity of the prostheses. There was no significant difference between pre-operative and post-operative range of motion for the entire group or between patients with broken or intact prostheses. Histological confirmation of silicone synovitis was documented in one patient who required implant removal. We suggest that destabilization and breakage of prostheses result from fatigue failure secondary to the torque generated at the distal radio-ulnar joint during repeated pronation and supination. Use of a silicone rubber ulnar head prosthesis following distal ulna resection is not recommended.


Rupture of extensor tendons due to osteoarthritis of the distal radio-ulnar joint.

Extensor tendons ruptured in 12 patients as a result of osteoarthritis of the distal radio-ulnar joint. Rupture occurred without warning in ten cases and was sequential in five. Perforation of the dorsal capsule of the distal radio-ulnar joint, allowing contact between the roughened ulnar head and extensor tendons, was present in every case. The capsular performation was demonstrated by arthrography, which may be used to identify patients who are at risk of extensor tendon rupture. Loss of independent extension of the little finger is a valuable clinical sign because rupture of extensor digiti minimi may be masked by a powerful contribution from the extensor tendon of the ring finger.


Natural history of scaphoid non-union, with special reference to "asymptomatic" cases.

33 patients with non-union of the carpal scaphoid were diagnosed by X-ray examination two to 37 years following the original trauma. All of the patients could be contacted and summoned for a re-examination ten to 17 years later. X-rays revealed a 100% incidence of progressive radio-carpal osteoarthritis. It is concluded that freedom of pain is not a reliable prognostic indicator, and that all patients with non-union of the carpal scaphoid are likely to benefit from surgical treatment of the pseudarthrosis. The only exception to this rule might be the patient in whom the radio-carpal joint is already deteriorated by an advanced degenerative arthritis.


Effects of dopamine agonist, bromocriptine, and some dopamine antagonists on ocular blood flow.

A dopamine agonist, bromocriptine, and several dopamine antagonists, domperidone, haloperidol, floropipamide and chlofluperol, were studied for their effects on the ocular blood flow. Both domperidone and haloperidol are ocular hypotensive agents and are able to increase the ocular blood flow significantly. Floropipamide had little effect on the intraocular pressure (IOP), yet it reduced the ocular blood flow markedly. Chlofluperol is an ocular hypertensive agent, yet it increased the ocular blood flow significantly. Although bromocriptine lowered the IOP, it did not affect the ocular blood flow. These results indicate that the changes of ocular blood flow are independent of the changes of the IOP. Therefore, it is critical to develop antiglaucoma agents which can increase retinal and choroidal blood flow in addition to lowering the IOP.


Inhibitory effect of tetrandrine on lens proteins-induced ocular inflammation in rabbits.

Ocular inflammation was induced by 25 microliters of lens proteins (62.5mg/ml) injected into anterior chamber of the rabbit eye. Tetrandrine (Tet) (50mg/kg ip) and Indomethacin (Ind) (20 mg/kg ip) showed marked inhibition on this ocular inflammation. Maximum inhibition rate of Tet and Ind was 65% and 66% and their anti-inflammation action lasted 5 and 4 h, respectively. In the early phase of ocular inflammation (at 2 h) the total content of prostaglandin E(PGES) in the iris was reduced by Tet and Ind. Ind showed a greater effect than Tet on PGES. Tet also inhibited leukocyte chemotaxis significantly at late phase of inflammation. No significant effect was observed on the IOP recovery following reduction by 20% NaCl iv. Topical instillation of 50 microliters of 2% Tet did not display any inhibition of ocular inflammation. These results indicate that Tet is an effective ocular antiinflammatory agent without producing ocular hypertension. The antiinflammatory mechanism of Tet in early phase (at 2 h) was related to inhibition of PGES synthesis. The relationship between ocular anti-inflammation and calcium antagonism of Tet was discussed.


Continuous flow contact lens delivery of gentamicin to rabbit cornea and aqueous humor.

The Morgan Therapeutic Lens (MTL) was investigated as a continuous corneal perfusion system in New Zealand white rabbits. Gentamicin concentration in the cornea and aqueous humor delivered by the MTL was compared to gentamicin drops (13.6 mg/ml) administered every 15 or 30 minutes. Gentamicin (1 mg/ml) or 5 mg/ml was perfused at 10 ml/hr for up to 4.0 hours. At each time interval of 0.5, 1, 2 and 4 hours, homogenized corneas and aqueous humour were assayed for gentamicin concentrations. The highest aqueous humour gentamicin concentrations of 57.99 +/- 12.86 micrograms/ml were significantly higher with the MTL and 5 mg/ml of gentamicin compared with the MTL and 1 mg/ml of gentamicin or than drops applied every 30 minutes, but not significantly different than drops every 15 minutes. Highest corneal concentrations of gentamicin of 496.04 +/- 101.16 micrograms/gm cornea were significantly higher with MTL and 5 mg/ml of gentamicin compared with the MTL and 1 mg/ml gentamicin or than drops applied every 30 minutes, but not significantly different than drops every 15 minutes. All mean gentamicin concentrations attained via the MTL exceeded the mean inhibitory concentration for most sensitive bacterial species. The MTL is a reliable drug delivery system with distinct advantages, and may be a useful therapeutic modality in the ocular delivery of gentamicin and other drugs.


THC:YAG laser sclerostomy with mitomycin subconjunctival injection in rabbits.

We performed sclerostomy using THC:YAG laser (thulium, holmium, chromium doped YAG crystal) and subconjunctival injection of mitomycin soon after the filtering process in rabbits to observe the lowering effect of intraocular pressure(IOP) and filtering bleb formation. A 1-mm conjunctiva wound was made 12 mm away from the sclerostomy site to allow the entry of the optic probe for delivering energy. Forty-eight rabbits were divided into 3 groups. After sclerostomy, Group I received 0.2 ml normal saline subconjunctival injection and Group II and III received 0.2 ml mitomycin injection of 0.1 and 0.2 mg/ml respectively. One eye of each rabbit was randomly selected for the experiment while the fellow eye served as control. The bleb lasted 1.4 +/- 0.5 days (or 1 to 2 days) in Group I, 8.5 +/- 4.5 days (or 4 to 17 days) in Group II and 15.4 +/- 10.9 days (or 4 to 37 days) in Group III. The IOP lowering effect was significantly enhanced in Group III. The postoperative complication was minimal corneal punctate erosion in the mitomycin group, but all of them, however, resolved within one week. The results demonstrated that mitomycin is effective in prolonging the filtering effect produced by the THC:YAG laser.


Prostaglandin synthesis and accumulation by porcine ciliary epithelium.

The activity to synthesize prostaglandins (PGs*) from arachidonic acid [i.e. cyclooxygenase (CO) activity] was compared between nonpigmented epithelial (NPE) cells and pigmented epithelial (PE) cells from porcine ciliary processes. PG synthesizing activities were about the same (0.58 and 0.52 pmol per mg protein per 15 min for NPE and PE, respectively), and inhibited by indomethacin and anti-CO antibody but not by nordihydroguaiaretic acid. By immunogold labeling, CO immunoreactivity was found both in NPE and PE. The present results and the previous observation on higher PG omega/omega-1 hydroxylation activities in NPE than in PE, taken together, suggest that controlled synthesis and inactivation of PGs may have a role in functions of NPE. When PGE2 was incubated with NPE or PE, NPE cells accumulated PGE2 more actively than did PE cells. PG uptake by the NPE cells may prevent aqueous and vitreous PGs from entering the anterior chamber and causing anterior uveitis.


Glucagon administration to the rat via eye drops.

Systemic absorption of glucagon from eye drops containing an emulsant caused an elevation in blood D-glucose concentrations in anesthetized rats. Glucagon (0.03 mg) delivered to the eye in buffered saline had no significant hyperglycemic action. However, delivery of glucagon in eye drops containing 0.25% saponin caused a rapid, dose-dependent increase in blood D-glucose values. Maximal absorption was observed 20 minutes after eye drop administration and values returned to baseline after 60 minutes. Immunoreactive glucagon levels measured 20 minutes after administration of eye drops containing saponin plus glucagon were increased by 2.4-fold compared to basal values. Glucagon administration via eye drops was ineffective when 0.5% Brij78 or BL-9 was substituted for saponin. These results demonstrate that in the rat, systemic absorption of glucagon delivered in eye drops is possible, but the choice of an emulsant may be critical.


The repertoire of human antibody to the Haemophilus influenzae type b capsular polysaccharide.

Human antibody to the Haemophilus influenzae capsular polysaccharide (Hib CP) is restricted in diversity in the individual and the population with a limited number of variable region genes encoding antibody. Antibody to the Hib CP shows restricted isoelectric focusing gel patterns and light chain usage with frequent restriction to use of only kappa light chains. Shared cross-reactive idiotypes are expressed on antibody. The heavy chain of antibody to the Hib CP is predominantly encoded by two members of the VH3 family--LSG 6.1/M85-like and VH26/30P1-like. In VH the CDR1, based on complete identity in LSG 6.1/M85-like antibodies, CDR2, based on the suggestion of mutation in this region, and CDR3, based on conserved CDR3 usage in unrelated individuals, may be important for antigen binding. Six or more different VL gene families encode antibody. The predominant antibody of the majority of individuals uses the A2-V kappa II gene in germline or near germline configuration, which encodes an idiotype designated HibId-1. Antibody can also be encoded by V kappa I, non-A2 V kappa II, V kappa III, V kappa IV, V lambda II, and V lambda VII genes. Although different VL genes can be used, unrelated individuals appear to use the same V kappa III (A27), V lambda II (V lambda 2.1 and V lambda VII (4A) genes. The VL diversity accounts for differences in fine binding specificity, with A2-V kappa II genes not encoding E. coli K100 CP cross-reactive antibodies and V lambda VII genes and some of the non-A2 V kappa genes encoding cross-reactive antibodies. The arginine in CDR3 of both antibody kappa and lambda light chains and the asparagine in CDR2 of VL sequences and in CDR1 of LSG6.1-M85 VH sequences of antibody appear to be important residues for antigen binding. A relatively limited degree of somatic mutation has occurred in the non-A2 VL genes, V lambda VII, and the VH genes. Further studies comparing the polymorphism of germline V genes to antibody-encoding V genes are needed to clarify this issue. Research comparing this repertoire to repertoires directed to other bacterial CP and to self antigens and defining structure-antigen binding relationships is in progress.


Human antibody responses to bacterial antigens: studies of a model conventional antigen and a proposed model B cell superantigen.

We have investigated the human antibody repertoires that bind to two different classes of bacterial antigens. Immunization with the conventional antigen, type b capsular polysaccharide of Haemophilus influenzae Hib PS, uniformly induces IgA and IgG responses dominated by clones that use heavy chains structurally related to two subsets of VH3 genes, while in a minority of subjects antibodies from the VH1 or VH4 families are co-induced. In contrast, the "alternative binding site" of Staphylococcal Protein A (SPA) represents an unconventional determinant, because; (i) SPA is bound by a large proportion of non-immune IgM, IgA and IgG F(ab')2, (ii) SPA is bound only to Fab from the VH3 family, which can be encoded by at least four different germline genes, (iii) SPA binding is independent of VL usage, (iv) by flow cytometry SPA is bound by > 15% of tonsilar B cells, but not to T cells. (v) In vitro stimulation with an SPA containing mitogen induces the preferentially production of Ig bearing a VH3 marker. Taken together, these studies characterize a VH family restricted binding interaction that is distinct from the properties associated with conventional antigens such as Hib PS. Based on these data we propose that SPA represents a prototype for a B cell superantigen.


Postoperative analgesia using a computerised infusion of alfentanil following aortic bifurcation graft surgery.

A Psion microcomputer controlled infusion system for alfentanil was assessed for the provision of post-operative analgesia in 14 patients who had undergone aortic bifurcation graft surgery. The system employed a pharmacokinetic model working in real time to deliver any selected target plasma concentration of alfentanil. The alfentanil infusion system was used for a mean time of 39 hours and for 96% of this time, patients were scored as having no pain or only mild pain. Severe pain was recorded for only 0.05% of the study time. The use of a pharmacokinetic delivery system may offer a convenient and simple method of providing postoperative analgesia with alfentanil.


Neonatal physiological trend monitoring by computer.

A premature baby born up to four months early is a fragile patient dependent on intensive care. The body systems are physiologically immature and so tolerate stress badly. The tendency of these infants to rapidly deteriorate, has led us to use a cotside computer monitoring system which displays physiological trends. Information from standard neonatal monitors is accessed by individual cotside PC's linked to a central network server and Doctors terminal. Trend graphs can be easily manipulated, displaying from 7 minutes to 3 days of physiological information on a single screen. Pathology may be observed in real time as it occurs. The system has 3 main areas of use, (a) as a real time clinical aid to patient management, e.g. apnoea of the newborn; (b) as a research tool, demonstrating the effects of procedures on physiology; (c) for educating members of staff about how physiological events develop. Data is saved for the whole of each neonates intensive care stay. Assessment of staff and parent attitudes by questionnaire have been favourable.


Acquisition of ICU data: concepts and demands.

As the issue of data overload is a problem in critical care today, it is of utmost importance to improve acquisition, storage, integration, and presentation of medical data, which appears only feasible with the help of bedside computers. The data originates from four major sources: (1) the bedside medical devices, (2) the local area network (LAN) of the ICU, (3) the hospital information system (HIS) and (4) manual input. All sources differ markedly in quality and quantity of data and in the demands of the interfaces between source of data and patient database. The demands for data acquisition from bedside medical devices, ICU-LAN and HIS concentrate on technical problems, such as computational power, storage capacity, real-time processing, interfacing with different devices and networks and the unmistakable assignment of data to the individual patient. The main problem of manual data acquisition is the definition and configuration of the user interface that must allow the inexperienced user to interact with the computer intuitively. Emphasis must be put on the construction of a pleasant, logical and easy-to-handle graphical user interface (GUI). Short response times will require high graphical processing capacity. Moreover, high computational resources are necessary in the future for additional interfacing devices such as speech recognition and 3D-GUI. Therefore, in an ICU environment the demands for computational power are enormous. These problems are complicated by the urgent need for friendly and easy-to-handle user interfaces. Both facts place ICU bedside computing at the vanguard of present and future workstation development leaving no room for solutions based on traditional concepts of personal computers.(ABSTRACT TRUNCATED AT 250 WORDS)


A knowledge-based system for assisted ventilation of patients in intensive care units.

The procedure for weaning a patient with respiratory insufficiency from mechanical ventilation may be complex and requires expertise obtained by long clinical practice. We designed a knowledge-based system for the management of patients receiving respiratory support and implemented a weaning procedure. The system is intended for patients whose spontaneous respiratory activity is assisted by a Hamilton Veolar ventilator delivering a positive pressure plateau during inspiration (Pressure Support Ventilation mode). Our closed-loop real-time system running on a Personal Computer continuously adapts the assistance provided by the ventilator to the patient's evolution, and indicates when the patient can be withdrawn from the ventilator. Three parameters are used to appreciate the 'respiratory comfort' of the patient: breathing frequency, which we consider the most informative index, tidal volume and end-tidal CO2 pressure. A preliminary study of 19 patients was performed to evaluate the ability of our system to adapt the assistance to the patient's needs, with the main objective of facilitating weaning by gradually lowering the level of assistance. In 10 of these patients, considered as good candidates for weaning on the strength of objective criteria, the system maintained the breathing pattern in a zone of comfort for 95% of the period of assisted ventilation and stated that they were 'weanable'. This was consistent with the clinical evolution of all 10 patients. These results show that such a system can provide effective management for mechanically ventilated patients.


Fuzzy classification of hemodynamic trends and artifacts: experiments with the heart rate.

Fuzzy set theory allows one to map inexact data, concepts, and events to fuzzy sets via user-defined membership functions. This paper describes a method for (1) robustly estimating the mean and slope of an arbitrary number of data points, (2) developing a set of fuzzy membership functions to classify various properties of heart rate trends, and (3) finding the longest consecutive sequence of heart rate data that fit a particular fuzzy membership function. Preliminary results indicate that fuzzy set theory has significant potential in the development of a clinically robust method for classifying heart rate data, trends, and artifacts.


A mechanosensitive K+ channel in heart cells. Activation by arachidonic acid.

Mechanosensitive ion channels have been described in many types of cells. These channels are believed to transduce pressure signals into intracellular biochemical and physiological events. In this study, the patch-clamp technique was used to identify and characterize a mechanosensitive ion channel in rat atrial cells. In cell-attached patches, negative pressure in the pipette activated an ion channel in a pressure-dependent manner. The pressure to induce half-maximal activation was 12 +/- 3 mmHg at +40 mV, and nearly full activation was observed at approximately 20 mmHg. The probability of opening was voltage dependent, with greater channel activity at depolarized potentials. The mechanosensitive channel was identical to the K+ channel previously shown to be activated by arachidonic acid and other lipophilic compounds, as judged by the outwardly rectifying current-voltage relation, single channel amplitude, mean open time (1.4 +/- 0.3 ms), bursty openings, K+ selectivity, insensitivity to any known organic inhibitors of ion channels, and pH sensitivity. In symmetrical 140 mM KCl, the slope conductance was 94 +/- 11 pS at +60 mV and 64 +/- 8 pS at -60 mV. Anions and cations such as Cl-, glutamate, Na+, Cs+, Li+, Ca2+, and Ba2+ were not permeant. Extracellular Ba2+ (1 mM) blocked the inward K+ current completely. GdCl3 (100 microM) or CaCl2 (100 microM) did not alter the K+ channel activity or amplitude. Lowering of intracellular pH increased the pressure sensitivity of the channel. The K+ channel could be activated in the presence of 5 mM intracellular [ATP] or 10 microM glybenclamide in inside-out patches. In the absence of ATP, when the ATP-sensitive K+ channel was active, the mechanosensitive channel could further be activated by pressure, suggesting that they were two separate channels. The ATP-sensitive K+ channel was not mechanosensitive. Pressure activated the K+ channel in the presence of albumin, a fatty acid binding protein, suggesting that pressure and arachidonic acid activate the K+ channel via separate pathways.


Two functionally distinct 4-aminopyridine-sensitive outward K+ currents in rat atrial myocytes.

In the experiments here, the detailed kinetic properties of the Ca(2+)-independent, depolarization-activated outward currents (Iout) in enzymatically dispersed adult rat atrial myocytes were studied. Although there is only slight attenuation of peak Iout during brief (100 ms) voltage steps, substantial decay is evident during long (10 s) depolarizations. The analyses here reveal that current inactivation is best described by the sum of two exponential components, which we have termed IKf and IKs to denote the fast and slow components, respectively, of Iout decay. At all test potentials, IKf inactivates approximately 20-fold more rapidly than IKs. Neither the decay time constants nor the fraction of Iout remaining at the end of 10-s depolarizations varies over the potential range of 0 to +50 mV, indicating that the rates of inactivation and recovery from inactivation are voltage independent. IKf recovers from inactivation completely, independent of the recovery of IKs, and IKf recovers approximately 20 times faster than IKs. The pharmacological properties of IKf and IKs are similar: both components are sensitive to 4-aminopyridine (1-5 mM) and both are relatively resistant to externally applied tetraethylammonium (50 mM). Taken together, these findings suggest that IKf and IKs correspond to two functionally distinct K+ currents with similar voltage-dependent properties and pharmacologic sensitivities, but with markedly different rates of inactivation and recovery from inactivation. From the experimental data, several gating models were developed in which voltage-independent inactivation is coupled either to channel opening or to the activation of the individual channel subunits. Experimental testing of predictions of these models suggests that voltage-independent inactivation is coupled to activation, and that inactivation of only a single subunit is required to result in functional inactivation of the channels. This model closely approximates the properties of IKf and IKs, as well as the composite outward currents, measured in adult rat atrial myocytes.


Minimum respiratory function for breath alcohol testing in South Australia.

The aim of this study was to determine if inability to complete a breath alcohol test successfully, using a Lion Alcolmeter SD-2 or Drager Alcotest 7110, was related to any of the standard parameters obtained from the lung function spirometry test. A total of 153 subjects referred to a clinical laboratory for routine lung function testing were tested using the Alcolmeter, 158 using the Alcotest, with 69 subjects completing tests on both instruments. Of the 153 patients who volunteered to use the Alcolmeter, 49 (32%) were unable to produce a valid test effort on this instrument. One subject failed to complete a satisfactory test using the Alcotest, and one was unable to master the technique. There was considerable overlap of the minimum value for each of the lung function parameters of those subjects who could or could not successfully complete the breath alcohol test. It is recommended that changes are made to both of the instruments, the techniques used and the legislation, to minimize the number of breath alcohol testing failures and to reduce the variability of the results.


Steady-state and dynamic properties of cardiac sodium-calcium exchange. Sodium-dependent inactivation.

Sodium-calcium exchange current was isolated in inside-out patches excised from guinea pig ventricular cells using the giant patch method. The outward exchange current decayed exponentially upon activation by cytoplasmic sodium (sodium-dependent inactivation). The kinetics and mechanism of the inactivation were studied. (a) The rate of inactivation and the peak current amplitude were both strongly temperature dependent (Q10 = 2.2). (b) An increase in cytoplasmic pH from 6.8 to 7.8 attenuated the current decay and shifted the apparent dissociation constant (Kd) of cytoplasmic calcium for secondary activation of the exchange current from 9.6 microM to < 0.3 microM. (c) The amplitude of exchange current decreased synchronously over the membrane potential range from -120 to 60 mV during the inactivation, indicating that voltage dependence of the exchanger did not change during the inactivation process. The voltage dependence of exchange current also did not change during secondary modulation by cytoplasmic calcium and activation by chymotrypsin. (d) In the presence of 150 mM extracellular sodium and 2 mM extracellular calcium, outward exchange current decayed similarly upon application of cytoplasmic sodium. Upon removal of cytoplasmic sodium in the presence of 2-5 microM cytoplasmic free calcium, the inward exchange current developed in two phases, a fast phase within the time course of solution changes, and a slow phase (tau approximately 4 s) indicative of recovery from sodium-dependent inactivation. (e) Under zero-trans conditions, the inward current was fully activated within solution switch times upon application of cytoplasmic calcium and did not decay. (f) The slow recovery phase of inward current upon removal of cytoplasmic sodium was also present under the zero-trans condition. (g) Sodium-dependent inactivation shows little or no dependence on membrane potential in guinea pig myocyte sarcolemma. (h) Sodium-dependent inactivation of outward current is attenuated in rate and extent as extracellular calcium is decreased. (i) Kinetics of the sodium-dependent inactivation and its dependence on major experimental variables are well described by a simple two-state inactivation model assuming one fully active and one fully inactive exchanger state, whereby the transition to the inactive state takes place from a fully sodium-loaded exchanger conformation with cytoplasmic orientation of binding sites (E1.3Ni).


Alleged sexual violation of a human female by a Rottweiler dog.

An unusual case involving the alleged sexual violation of a woman by three men and a Rottweiler dog is described. Forensic examination proved difficult and showed little of evidentiary value but did reveal the presence of dog hairs at the scene, and semen from one of the men on the victim's panties. All attempts to locate and identify dog semen were unsuccessful. It was not clear whether dog semen could not be located using available techniques for semen identification, or whether dog semen was, in fact, not present at all.


Steady-state and dynamic properties of cardiac sodium-calcium exchange. Secondary modulation by cytoplasmic calcium and ATP.

Dynamic responses of cardiac sodium-calcium exchange current to changes of cytoplasmic calcium and MgATP were monitored and analyzed in giant membrane patches excised from guinea pig myocytes. Secondary dependencies of exchange current on cytoplasmic calcium are accounted for in terms of two mechanisms: (a) The sodium-dependent inactivation process, termed I1 modulation, is itself strongly modulated by cytoplasmic calcium. Recovery from the I1 inactivated state is accelerated by increasing cytoplasmic calcium, and the calculated rate of entrance into I1 inactivation is slowed. (b) A second modulation process, termed I2 modulation, is not sodium dependent. As with I1 modulation, the entrance into I2 inactivation takes place over seconds in the absence of cytoplasmic calcium. The recovery from I2 inactivation is a calcium-dependent transition and is rapid (< 200 ms) in the presence of micromolar free calcium. I1 and I2 modulation can be treated as linear, independent processes to account for most exchange modulation patterns observed: (a) When cytoplasmic calcium is increased or decreased in the presence of high cytoplasmic sodium, outward exchange current turns on or off, respectively, on a time scale of multiple seconds. (b) When sodium is applied in the absence of cytoplasmic calcium, no outward current is activated. However, the full outward current is activated within solution switch time when cytoplasmic calcium is applied together with sodium. (c) The calcium dependence of peak outward current attained upon application of cytoplasmic sodium is shifted by approximately 1 log unit to lower concentrations from the calcium dependence of steady-state exchange current. (d) The time course of outward current decay upon decreasing cytoplasmic calcium becomes more rapid as calcium is reduced into the submicromolar range. (e) Under nearly all conditions, the time courses of current decay during application of cytoplasmic sodium and/or removal of cytoplasmic calcium are well fit by single exponentials. Both of the modulation processes are evidently affected by MgATP. Similar to the effects of cytoplasmic calcium, MgATP slows the entrance into I1 inactivation and accelerates the recovery from inactivation. MgATP additionally slows the decay of outward exchange current upon removal of cytoplasmic calcium by 2-10-fold, indicative of an effect on I2 inactivation. Finally, the effects of cytoplasmic calcium on sodium-calcium exchange current are reconstructed in simulations of the I1 and I2 modulation processes as independent reactions.


An investigation of the feasibility of inferring ethnic origin from DNA profiles.

A small experiment is described which uses databases of Afro-Caribbeans and Caucasians to establish the quality of information that might be given to an investigator about the ethnic group of the donor of an unknown crime stain. The results show that the technique can provide qualified indications, but categoric conclusions are not, in general, feasible. An appraisal is given of the technique within the operational context.


Oral sex--further information from sexual assault cases.

A survey was carried out of sexual assault cases submitted to the Metropolitan Police Forensic Science Laboratory during 1988 and 1989. There were 104 cases with male victims, and 1403 with females. In the all-male offences, fellatio was reported in 34%; nearly two-thirds of the acts were by the offender, one-third by the victim. In the offences on females, oral-genital acts were alleged in 22%, 78% of which were fellatio, and 22% cunnilingus. The majority of offenders were white. The few Afro-Caribbeans studied rarely performed oral sex on males or very young females.


Comparison of location, severity, and dose response of proximal axonal lesions induced by 3,3'-iminodipropionitrile and deuterium substituted analogs.

Administration of 3,3'-iminodipropionitrile (IDPN) to rats results in massive accumulation of tangled neurofilaments in the proximal axons of large neurons, such as in dorsal root ganglia (DRG) and ventral horns of the lumbar spinal cord (LSC). Clinically, rats develop hyperexcitability, circling, head bobbing, and retropulsion. The ultimate toxicant and the molecular mechanism are not known. In a study designed to explore potential activation and detoxification pathways, dose-related differences in location and severity of lesions were observed in rats treated with IDPN or deuterium substituted analogs, 2,2,2',2'-tetradeuterio-IDPN (2-d-IDPN) or 3,3,3',3'-tetradeuterio-IDPN (3-d-IDPN). The compounds or saline were administered intraperitoneally to three rats per group at dose levels of 3.0, 1.5, 1.0, and 0.0 mmole/kg/day for 3 days. One week after the initial dose, tissues from DRG and LSC were collected, prepared and evaluated histologically in zones extending from areas adjacent to the cell bodies, distally toward the DRG stalk or toward the lumbar spinal roots. In the low dose IDPN group, DRG and LSC lesions were most prominent in distal zones. As dosage increased, the lesions progressed in severity and in proximity to the cell bodies. At the high dose, lesions were prominent in all zones. The same general pattern occurred with both analogs, although 2-d-IDPN was less potent than IDPN and 3-d-IDPN was more potent than IDPN. The differences in potency from the secondary isotopic effect of deuterium suggest that the 3-position is important in detoxification while the 2-position is important in the bioactivation of IDPN.


Sudden infant death syndrome: postnatal changes in the numerical density and total number of neurons in the hypoglossal nucleus.

Tissue specimens from the medulla were sampled from 28 sudden infant death syndrome (SIDS) victims and from 15 control cases without neurological disease (36-95 postconceptional weeks). Morphometric analyses were performed on serial Nissl sections through the hypoglossal nucleus. The total volume of the hypoglossal nucleus, the numerical density (Nv, cells per mm3) and the total number of motor neurons, interneurons and glia were determined. Normal development was characterized by a linear increase in the volume of the hypoglossal nucleus during the first postnatal year. While the Nv of neurons decreased, the total number of neurons remained relatively constant at approximately 7,600 motor neurons and 3,100 interneurons. In SIDS cases the rate of increase in the volume of the hypoglossal nucleus was significantly greater than in controls (79%). The Nv of neurons was less than in controls (25-30%), although the total number of motor neurons and interneurons did not differ significantly. In SIDS cases the mean profile area of motor neuron cell bodies was significantly greater than in controls (29%), while the mean profile areas of interneurons and glia did not differ. These abnormalities in growth indicate a greater volume of neuropil in a hypoglossal nucleus containing a normal complement of neurons. The disproportionately rapid increase in volume of neuropil in the hypoglossal nucleus of SIDS cases may result from an increased arborization of dendrites on the motor neurons.


Selective neuronal vulnerability in HIV encephalitis.

Recent studies of human immunodeficiency virus type 1 (HIV-1) encephalitis have shown that in addition to well established white matter damage, the neocortex shows thinning, loss of large neurons and dendritic damage. In order to identify neuronal populations affected in HIV encephalitis and to determine how neuronal damage relates to the severity of HIV infection within the nervous system, we quantified parvalbumin (PV+) and neurofilament (NF+) immunoreactive neurons in the frontal cortex and hippocampus. We found that in the neocortex, the density of NF+ and PV+ neurons was independent of severity of HIV encephalitis, and therefore changes in these neuronal subsets did not account for previously reported neuronal loss. However, neuritic processes of PV+ neurons were fragmented, atrophic and in some cases distended. In contrast to the frontal cortex, there was a trend toward decreased density of PV+ neurons in the hippocampus which only reached significance in the CA3 layer where there was a 50-90% decrease in PV+ neurons. This decrease was closely correlated with the severity of HIV encephalitis. Double-label immunocytochemical analysis confirmed neuritic damage to interneurons. These results suggest that HIV encephalitis differentially involves specific subpopulations of neurons. Since direct HIV infection of neuronal cells was not detected, damage to PV+ cells and fibers may be indirectly mediated by cytokines released by HIV-infected microglia.


The development of induced cerebrocortical microgyria in the rat.

Placement of a freezing probe on the skull of neonatal rats produces four-layered microgyria, complete with a lamina dissecans and microsulcus. We studied the developmental course of this induced microgyria under light microscopy by examining changes in neurons, glia, and macrophages following a focal freezing insult on the day of birth (postnatal day [P]0). The destruction of neurons and glia induced by the freezing probe extends through the cortical plate and occasionally through the subplate, but the pial membrane appears undamaged and radial glial cells, while damaged, are not eliminated. Reactive astrocytes and macrophages arrive in the damaged area within 24 hours of the injury, and repair of the damaged tissue peaks within the first week. Damaged radial glial fibers regrow, and supragranular neurons migrate through this damaged area, also within the first week. The newly formed supragranular layer overlies the cell-free area. The damaged cortex begins to assume its adult-like microgyric appearance from P5 to P10. On P15 and P32, long glial fibers, resembling radial glia, are present and are immunoreactive for glial fibrillary acidic protein and radial glial fiber antibodies (vimentin and Rat-401). No such fibers appear at this age in the non-microgyric areas or in normal brains. We conclude that microgyria formation may be the consequence of brain repair mechanisms occurring during neuronal migration to the neocortex, and that it appears to preserve primitive features characteristic of the developing cortex.


Innervation of the vasa nervorum: changes in human diabetics.

Transperineurial and epineurial vessels are innervated by plexuses of unmyelinated axons. Human sural nerve biopsies were examined ultrastructurally and immunocytochemically with an antibody which recognizes a neuronal and neuroendocrine protein, PGP 9.5, to characterize perivascular axons of these plexuses. Diabetics exhibited a greater degree of abnormal innervation of the vasa nervorum than nondiabetics with and without neuropathy. Abnormal innervation included: a reduction in the percentage of vessels exhibiting perivascular axons and a concomitant increase in the percentage of vessels having denervated Schwann cell units, particularly around vessels confined to perineurial compartments, and remaining axons in nerves from diabetics exhibited fewer varicosities. Denervated arterioles of diabetics also displayed structural changes indicating injury. The arteriolar structural defects and loss of neurogenic control of neural blood flow may lead to or aggravate endoneurial ischemia or hypoxia. The patchy, focal endoneurial fiber loss that is prominent in proximal nerves and associated with the distal myelinated fiber loss of some diabetic patients may be due in part to perivascular denervation of the vasa nervorum.


Parenting classes: focus on discipline.

Nurses in community settings have an opportunity to provide instruction related to health and life-style needs. An important consideration is the parental role. A particularly controversial and opinion-laden aspect of parenting is disciplining children. Discipline provides children with the security of clearly enforced rules to help them learn self-control and social standards. Parenting classes are worthwhile for people who have little formal or informal preparation. A survey of middle-class elementary school district parents' and childrens' attitudes toward discipline was conducted to develop meaningful parenting classes. Parents' feelings about being a mother or father were surprisingly negative. A parent educational program was developed to cover child growth and development and disciplinary practices. Parent evaluations led to continuation and an expansion of this program to other schools within the area.


Community health assessment tool: a patterns approach to data collection and diagnosis.

Creation of an assessment tool to apply Gordon's functional patterns to the community as a client was a rewarding and stimulating project. Through use of the CHAT, students developed an appreciation of the complexity and inter-relationship of numerous aspects of the community. They completed the nursing process by developing appropriate nursing diagnoses, and planning, implementing, and evaluating a health promotion project. As the students continue to use this tool in the health promotion course, the diagnoses which they generate are being collected. From this accumulated input the plan is to compile a list of common diagnoses which are appropriate to use when the community is the client.