The manufacture of generic replicas of implants for arthroplasty of the hip and knee: is it regulated and will it save money?

Joint replacement of the hip and knee remain very satisfactory operations. They are, however, expensive. The actual manufacturing of the implant represents only 30% of the final cost, while sales and marketing represent 40%. Recently, the patents on many well established and successful implants have expired. Companies have started producing and distributing implants that purport to replicate existing implants with good long-term results. The aims of this paper are to assess the legality, the monitoring and cost saving implications of such generic implants. We also assess how this might affect the traditional orthopaedic implant companies. Cite this article: Bone Joint J 2016;98-B:892-900.

Giant adrenal myelolipoma: a case report.

Adrenal myelolipomas are rare, benign, hormonally inactive tumours composed of mature adipose tissue and haematopoietic elements. Currently, most diagnosed tumours are discovered incidentally because of modern imaging. Myelolipomas are usually asymptomatic, but symptoms such as abdominal pain, haematuria and abdominal mass are described as the result of tumour bulk, haemorrhage or tumour necrosis. Myelolipomas are usually small, although there are descriptions of giant myelolipomas in the literature. We report the case of a giant adrenal myelolipoma in a 79-year-old female who presented with epigastric pain and discomfort. The resected tumour weighed 1777 g and measured 20.5 x 18 x 9.0 cm.

A decade of salpingoscopy.

With the introduction of the salpingoscopy of the tubal ampullary mucosa in the 1980s, this diagnostic endoscopic examination not only disclosed an exciting world of sharp and detailed in vivo images of the actual site of human fertilization. Its systematic use in the assessment of the tubal factor in subfertile couples also provides specific, clinically relevant and prognostically valuable information, since it clearly demonstrates the presence or absence of anatomical distortions, especially adhesions between and destruction of mucosal folds, on a micro-endoscopic, i.e., mucosal level. The routine salpingoscopy of a free, patent tube is easy to perform and the procedure then takes about 10 min for both sides. In contrast with hysterosalpingography, a proximal (e.g., tubocornual or isthmic) block does not prevent us from examining the ampullary mucosa with the salpingoscope, whereas a small incision at the site of the occlusion with one of the techniques of operative laparoscopy, enables the inspection of the mucosa of a hydrosalpinx. With salpingoscopy, and using a simple classification system, a trained endoscopist can evaluate the sequelae of tubal inflammatory disease and their impact on fertility nearly as efficiently as with mucosal microbiopsies and they can direct their patients accordingly, either towards reconstructive (micro)surgery or towards medically assisted reproduction. In case of a tubal pregnancy, the effort to salpingoscopically evaluate both the affected and unaffected side may help to understand the underlying ethiology of the ectopic. Since patency and a normal appearance of the fimbriated end surely do not imply the absence of endoluminal pathology, it is advisable to select only salpingoscopically normal tubes to perform tubal transfers of gametes, zygotes or embryos. In the still ongoing discussion regarding preventive salpingectomy prior to IVF-ET in case of a uni- or bilateral hydrosalpinx, blind victimization of the Fallopian tube can in our opinion be avoided by a proper endoscopic selection of cases.

A patient with unique bilateral ovarian metastases 11 years after the treatment of breast cancer.

We report a patient in whom 11 years after the treatment of a breast tumour, bilateral ovarian metastases were disclosed. Surgical exploration confirmed unique ovarian metastases within a 'clean' abdomen and pelvis. The particularities of this case compared with the literature are the rather long interval of 11 years and the fact that no other metastases were present. The literature indeed reveals that most of the patient with ovarian metastases are premenopausal, have bilateral involvement; the ovarian metastases occur within a few years and are frequently accompanied by other metastases.

Clinical value and cumulative pregnancy rates following rigid salpingoscopy during laparoscopy for infertility.

This study was designed to evaluate the routine use of rigid salpingoscopy during diagnostic laparoscopy for infertility, and to relate the morphologic image of the endosalpinx with pregnancy outcome. A total of 158 consecutive patients (232 Fallopian tubes) undergoing a diagnostic laparoscopy for infertility were studied. Salpingoscopy was performed at the time of diagnostic laparoscopy for infertility. The intraluminal image was classified using a simplified classification (class I-V). The relationship between this classification and the cumulative pregnancy rates was calculated using life table analysis. Patients with a normal salpingoscopy (class I and II) had a 71% cumulative pregnancy rate. In the intermediate group (class III) the cumulative pregnancy rate was 34%. No intrauterine pregnancies were observed in the group with severe intratubal pathology (class IV and V). Of the 107 slapingoscopies of patients with endometriosis 105 (98%) were class I or II. However, among patients with pelvic adhesions, only 42% were normal. Nine out of 50 abnormal salpingoscopies were found when no tubal factor was suspected during laparoscopy, without any pelvic adhesions. These results suggest that salpingoscopy is an important tool for detecting mucosal abnormalities, and for eventually referring patients for assisted reproductive technology. Salpingoscopy is usually normal in patients with endometriosis, but in patients with non-endometriotic pelvic adhesions it is not.

A non-hodgkin-lymphoma of the breast, occurring 20 years after the treatment of a hodgkins-disease.

We report on a woman in whom the fortuitous diagnosis of a non-Hodgkin lymphoma of the breast was made. She had been treated 20 years earlier elsewhere for Hodgkin's disease stage III. The remarkable association of an extranodal lymphoma with a previously treated Hodgkin's disease is discussed.

Polycystic ovarian disease treated by laparoscopic argon laser capsule drilling: comparison of vaporization versus perforation technique.

Forty-four anovulatory women with polycystic ovarian disease (PCOD) were laparoscopically treated with the argon laser. Eighty percent of them were previously resistant to clomiphene citrate therapy. After surgery spontaneous ovulation occurred in 80% of the women. Spontaneous conception occurred in 55% of patients, and another 18% of the women who were previously resistant to clomiphene citrate conceived post-operatively after clomiphene citrate therapy. This gives an overall conception rate of 73% after 18 months (using life table analysis). Two different drilling techniques were used: classical vaporization of the ovarian capsule (22 women), and simple perforation of the ovarian capsule with subcapsular destruction of the ovarian stroma (22 women). No different ovulation or pregnancy rates were observed post-operatively between the two techniques. These results suggest that patients with PCOD can be induced to ovulate, and subsequently conceive, by laparoscopic argon laser treatment. The technique with minimal trauma to the ovarian capsule seems preferable.

Risperidone as add-on therapy in behavioural disturbances in mental retardation: a double-blind placebo-controlled cross-over study.

A double-blind placebo-controlled cross-over trial was carried out to evaluate the efficacy and safety of the combined serotonin-dopamine antagonist risperidone in mentally retarded patients with persistent behavioural disturbances. After an observation period of 1 week, risperidone 4-12 mg or placebo was administered during 3 weeks as add-on treatment to the existing medication, followed by a 1-week single-blind placebo wash-out, and another 3 weeks of double-blind treatment with the cross-over medication. Thirty-seven patients participated in the trials; 30 completed the study. Risperidone was significantly superior to placebo in its effect on the Aberrant Behaviour Checklist and the Clinical Global Impression. The Extrapyramidal Symptom Rating Scale did not show any differences between risperidone and placebo. Two patients experienced hypotension at the start of the risperidone administration. Sedation and drowsiness were the most frequently reported treatment-emergent adverse events. The results of this trial warrant further investigation into the therapeutic assets of risperidone in this indication, as add-on therapy and as monotherapy.

Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study.

Forty-four chronic schizophrenic inpatients participated in this multicentre 12-week parallel-group double-blind trial. After a run-in period of 2 weeks and a single-blind placebo wash-out of 1 week, they were randomly assigned to treatment with either the serotonin2 and dopamine-D2 antagonist risperidone or haloperidol. Two patients were excluded from the efficacy analysis. Five patients dropped out in the haloperidol group and 1 in the risperidone group. At the end of the trial, the mean daily dose was 12 mg for risperidone and 10 mg for haloperidol. The risperidone group showed greater improvement on the Positive and Negative Syndrome Scale for Schizophrenia, the Schedule for Affective Disorders and Schizophrenia-change version, and the Nurses' Observation Scale for Inpatient Evaluation. The improvement of negative symptoms was more pronounced in the risperidone group until week 8 of double-blind treatment. The consumption of antiparkinsonian medication was 10 times lower with risperidone. Both drugs were well tolerated and the laboratory, endocrinological and cardiovascular safety parameters were comparable. This study suggests that risperidone is comparable to haloperidol as an antipsychotic, but that it has a safer EPS profile.

Ventricular enlargement, clinical correlates and treatment outcome in chronic schizophrenic inpatients.

The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared with that of 42 age-matched medical controls. For the schizophrenics, the relationship of various clinical parameters to the VBR was assessed, and the outcome of 12 weeks of double-blind treatment with either risperidone or haloperidol. The results confirm that schizophrenic patients have slightly enlarged lateral ventricles compared with medical controls. Only for schizophrenics, an effect of age, but not of duration of illness, was noticed. This study does not support the validity of a clinical subdivision of chronic schizophrenic patients on the basis of the VBR. Neither negative, positive nor general psychopathological symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were abnormal involuntary movements or extrapyramidal symptoms. No association between season of birth or a family history of major mental disorder and VBR could be demonstrated. Treatment response was predicted by the total PANSS score and the PANSS general psychopathology subscale score at baseline. There was a trend for patients with higher VBR to have a more or haloperidol). or haloperidol).

Pilot clinical investigation of risperidone in the treatment of psychotic patients.

Sixty-one adult psychotic patients were treated for four weeks in an open dose-finding study with the new combined serotonin-dopamine antagonist risperidone (R 64 766). Risperidone had a rapid onset of action; a highly significant decrease in the total score on the Brief Psychiatric Rating Scale (BPRS) was already noticed after the first week of treatment. There was also a significant decrease in score for individual BPRS items related to positive, negative, and affective symptoms. In spite of the withdrawal of antiparkinson medication at selection, a significant decrease in extra-pyramidal symptoms (EPS) was observed, as assessed on the Simpson and Angus Scale. The Clinical Global Impression of therapeutic effect was consistent with the BPRS scores, showing a constant improvement throughout the study. The mean daily dose of risperidone at the end of the study was 3.7 mg. Tolerance was excellent and only mild side-effects were reported. Vital signs, ECG-parameters, and laboratory values remained within normal limits. This study demonstrates that risperidone has great potential as an effective and well-tolerated alternative for the treatment of chronically psychotic patients. It has potent antipsychotic effects, a low EPS-inducing profile, and, at the same time, it improves the negative and affective symptoms of schizophrenia.

El desarrollo de nuevas drogas antipsicoticas / Development of new antipsychotic drugs

Se da por sentado que en la esquizofrenia, los efectos terapéuticos de los neurolépticos se basan en el bloqueo de los receptores de dopamina situados en el cerebro. Sin embargo, también se admite que los neurolépticos "clásicos" presentan algunos incovenientes importantes: su relativa falta de efectos sobre los síntomas negativos y su capacidad de inducción de síntomas extrapoiramidales (SEP). Experiencias clínicas llevadas a cabo con pipamperona mostraron que un antagonista combinado de serotinina 5-HT2 y dopamina D2 presentaba ventajas en el tratamiento de la esquizofrenia. Esto se hizo patente a través de los efectos antiautísticos observados, de la regulación de los ritmos de sueño y de vigilia perturbados y de la baja tendencia a la inducción de SEP. Los estudios realizados con setoperona, compuesto de perfil farmacológico comparable, confirmaron estas observaciones. No se pudo explorar la exacta implicación del antagnista 5-HT2 en los tratamientos psicofarmacológicos de la esquizofrenia hasta no haberse realizado la síntesis del receptor antagonista selectivo y específico: la ritanserina. En efecto las pruebas de doble ciego efectuadas demostraron una majoría sensible de los síntomas negativos y extrapiramidales. Puesto que las ventajas de la monoterapia en el tratamiento de la esquizofrenia son innegables, lo lógico era pasar a la selección de un compuesto con un antagonismo central comparable al de...

El desarrollo de nuevas drogas antipsicoticas / Development of new antipsychotic drugs

Se da por sentado que en la esquizofrenia, los efectos terapéuticos de los neurolépticos se basan en el bloqueo de los receptores de dopamina situados en el cerebro. Sin embargo, también se admite que los neurolépticos "clásicos" presentan algunos incovenientes importantes: su relativa falta de efectos sobre los síntomas negativos y su capacidad de inducción de síntomas extrapoiramidales (SEP). Experiencias clínicas llevadas a cabo con pipamperona mostraron que un antagonista combinado de serotinina 5-HT2 y dopamina D2 presentaba ventajas en el tratamiento de la esquizofrenia. Esto se hizo patente a través de los efectos antiautísticos observados, de la regulación de los ritmos de sueño y de vigilia perturbados y de la baja tendencia a la inducción de SEP. Los estudios realizados con setoperona, compuesto de perfil farmacológico comparable, confirmaron estas observaciones. No se pudo explorar la exacta implicación del antagnista 5-HT2 en los tratamientos psicofarmacológicos de la esquizofrenia hasta no haberse realizado la síntesis del receptor antagonista selectivo y específico: la ritanserina. En efecto las pruebas de doble ciego efectuadas demostraron una majoría sensible de los síntomas negativos y extrapiramidales. Puesto que las ventajas de la monoterapia en el tratamiento de la esquizofrenia son innegables, lo lógico era pasar a la selección de un compuesto con un antagonismo central comparable al de... (AU)

[Development of new antipsychotic drugs]. / El desarrollo de nuevas drogas antipsicóticas.

As far as schizophrenia is concerned, therapeutical effects of neuroleptics based on brain-located dopamine receptor blockers are taken for granted. It is also admitted, however, that classical neuroleptics have inconveniences, namely: Their relative lack of effect on negative symptoms, and their liability to induce extrapyramidal symptoms (EPS). Pipamperone-based clinical studies evidenced that an antagonist combining serotonin 5-HT2, and dopamine D2 was successful in the treatment of schizophrenia--which could be clearly observed in (a) anti-autistic effects, (b) regulating disrupted sleep-wake rhythms, and (c) a lesser tendency to EPS. Setoperone-based studies--a compound with a comparable pharmacological profile--confirmed the above observations. Until, however, the synthesis of ritanserin--a specific, and selective antagonistic receptor--was not achieved, no exact implication of 5-HT2 antagonist in psychopharmacological treatments of schizophrenia could be explored further. Indeed, double-blind trials evidenced a remarkable improvement in negative as well as extrapyramidal symptoms. Since a monotherapy appeared as undeniably called for in the treatment of schizophrenia, the next logical step to be taken was selecting a compound with a central antagonism comparable to ritanserin's, and a central D2 antagonism comparable to haloperidol's. Among a chemical range of benzisoxazole derivatives, risperidone was thus selected. The first double-blind trials on chronic schizophrenic patients seem indeed to confirm that this substance is likely to get over the above mentioned inconveniences, so typical of classical neuroleptics.

El desarrollo de nuevas drogas antipsicóticas. / [Development of new antipsychotic drugs]

As far as schizophrenia is concerned, therapeutical effects of neuroleptics based on brain-located dopamine receptor blockers are taken for granted. It is also admitted, however, that classical neuroleptics have inconveniences, namely: Their relative lack of effect on negative symptoms, and their liability to induce extrapyramidal symptoms (EPS). Pipamperone-based clinical studies evidenced that an antagonist combining serotonin 5-HT2, and dopamine D2 was successful in the treatment of schizophrenia--which could be clearly observed in (a) anti-autistic effects, (b) regulating disrupted sleep-wake rhythms, and (c) a lesser tendency to EPS. Setoperone-based studies--a compound with a comparable pharmacological profile--confirmed the above observations. Until, however, the synthesis of ritanserin--a specific, and selective antagonistic receptor--was not achieved, no exact implication of 5-HT2 antagonist in psychopharmacological treatments of schizophrenia could be explored further. Indeed, double-blind trials evidenced a remarkable improvement in negative as well as extrapyramidal symptoms. Since a monotherapy appeared as undeniably called for in the treatment of schizophrenia, the next logical step to be taken was selecting a compound with a central antagonism comparable to ritanserins, and a central D2 antagonism comparable to haloperidols. Among a chemical range of benzisoxazole derivatives, risperidone was thus selected. The first double-blind trials on chronic schizophrenic patients seem indeed to confirm that this substance is likely to get over the above mentioned inconveniences, so typical of classical neuroleptics.

The efficacy of the D2 and 5-HT2 antagonist risperidone (R 64,766) in the treatment of chronic psychosis. An open dose-finding study.

After a wash-out period of 1 week, 20 patients suffering from schizophrenia were treated for 4 weeks in an open dose-finding study with a new serotonin-dopamine antagonist risperidone. All patients completed the trial. The mean daily dose of risperidone was 4.6 mg (range 2-10 mg) at completion. Risperiodone had a rapid onset of action: a highly significant decrease of the total BPRS score (Brief Psychiatric Rating Scale) was already noticed at the end of the second week. This decrease was found in all BPRS factors after 4 weeks. In spite of the withdrawal of antiparkinson medication at selection, a clear decrease of EPS (extrapyramidal symptoms), assessed on the Simpson and Angus Scale, was observed. The Global Therapeutic Impression agreed to the BPRS scores, showing a highly significant improvement after 2 weeks of treatment. Risperidone was very well tolerated, only mild side effects were reported. Vital signs, electrocardiographic parameters and laboratory values remained normal during the trial. This study indicates that risperidone can be an effective and well-tolerated alternative in the treatment of chronic schizophrenia, combining an antipsychotic activity, a beneficial effect on anergia and anxiety depression and a low EPS-inducing profile.

Therapeutic effect and safety of increasing doses of risperidone (R 64766) in psychotic patients.

Risperidone (R 64766) was administered during 4 weeks in increasing doses to 17 psychotic patients, to evaluate the hematological and cardiovascular safety, the therapeutic effect, side effects, effects upon endocrinological parameters and the pharmacokinetic profile. Following a placebo wash-out period of 1 week, the initial dose was 10 mg daily, increasing with 5 mg per week until the maximal dose of 25 mg daily was reached during the 4th week of treatment. Doses up to 20 mg daily resulted in a significant improvement of the total BPRS score and of the different BPRS factor scores; with higher doses, no further clinical benefit was achieved except for the hostility and anxiety-depression factor, while sedation became more prominent. No increase of extrapyramidal symptoms was noticed. Except for the sedation observed with higher doses, risperidone was well tolerated. No clinically relevant effects on cardiovascular and ECG parameters were noticed, and except for a slight increase of aspartate aminotransferase and alanine aminotransferase in one patient, no laboratory abnormalities were observed. Prolactin showed an expected increase, while the other endocrinological parameters revealed no changes. Risperidone had a linear pharmacokinetic profile.

Risperidone (R64 766) in psychotic patients. A first clinical therapeutic exploration.

Seventeen therapy-resistant adult male psychotic inpatients were treated in an exploratory open study with the new combined serotonin-S2 and dopamine-D2 antagonist risperidone (R 64 766). The mean daily dose was 4.5 mg orally, and the mean duration of treatment 6 months. There were 11 responders, 5 non-responders and 1 drop-out. Risperidone combined an effective antidelusional potency with important contact- and mood-improving properties, while at the same time it reduced existing extrapyramidal symptoms (EPS). Three out of the 5 non-responders were probably underdosed. Risperidone was very well tolerated, reported side effects were mild and transient, and no reason for premature interruption of the therapy.