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Biomedical subjects

P P Griffin

Publications and source records attributed to P P Griffin.

At least 19 recordsLinked to original sources

The cerebral palsied hip.

Controversy exists regarding the role of pelvic obliquity in hip dysplasia and cerebral palsy. Earlier authors noted such a relationship but did not confirm its existence by scientific study. The current study confirms the association of pelvic obliquity to hip dysplasia in spastic cerebral palsy. At presentation of subluxation or dislocation before surgery, 80 patients were indexed into 5 body alignment types. Reclassifications were performed with passage of time to study the natural history and effects of surgery. Hip dysplasia was found in all cases to be consistent with the forces related to pelvic obliquity.

Cerebral Palsy↗

Shortening in femoral shaft fractures in children treated with spica cast.

Early spica cast treatment is one method used for children's femoral shaft fractures; it is increasingly advocated as treatment that allows early hospital discharge. The outcome of early spica cast treatment in 100 children, ages 2 to 10 years, with uncomplicated and isolated closed femoral shaft fractures treated at Johns Hopkins Hospital between October 1987 and March 1994 were analyzed. The objective was to identify those children who can be treated safely and dependably with early spica casting without excessive shortening of the fracture fragments. Eighty-one (81%) children had an acceptable outcome and 19 (19%) had an unacceptable outcome by the definition of more than 25 mm of fracture fragment overlap after clinical healing. A new clinical test, the telescope test, was statistically significant for correlation with spica cast outcome. Age, gender, fracture, location, mechanism of injury, fracture type, and resting radiograph of fracture fragment overlap were not statistically significant. The telescope test had a sensitivity of 80% and a specificity of 85% for predicting outcome. The relative risk for failure of spica cast treatment with a positive telescope test was 20.4 (95% confidence limits = 2.7-225.1). Children 2 to 10 years of age with uncomplicated femoral shaft fractures and a negative telescope test can be treated appropriately in most cases with early application of a spica cast.

Casts, Surgical↗

Bladder preservation by combined modality therapy for invasive bladder cancer.

PURPOSE: To update the efficacy of a selective multimodality bladder-preserving approach by transurethral resection (TURBT), systemic chemotherapy, and radiation therapy. PATIENTS AND METHODS: From 1986 through 1993, 106 patients with muscle-invading clinical stage T2 to T4a,Nx,M0 bladder cancer were treated with induction by maximal TURBT and two cycles of chemotherapy (methotrexate, cisplatin, vinblastine [MCV]) followed by 39.6-Gy pelvic irradiation with concomitant cisplatin. Patients with a negative postinduction therapy tumor site biopsy and cytology (a T0 response, 70 patients) plus those with less than a T0 response but medically unfit for cystectomy (six patients), received consolidative chemoradiation to a total of 64.8 Gy. Surgical candidates with less than a T0 response (13 patients) and patients who could not tolerate the chemoradiation (six patients) went to immediate cystectomy. The median follow-up duration is 4.4 years. RESULTS: The 5-year actuarial overall survival and disease-specific survival rates of all patients are 52% and 60%, respectively. For clinical stage T2 patients, the actuarial overall survival rate is 63%, and for T3-4, 45%. Thirty-six patients (34%) underwent cystectomy, all with evidence of tumor activity, including 17 with an invasive recurrence. The 5-year overall survival rate with an intact functioning bladder is 43%. Among 76 patients who completed bladder-preserving therapy, the 5-year rate of freedom from an invasive bladder relapse is 79%. No patient required cystectomy for treatment-related bladder morbidity. CONCLUSION: Combined modality therapy with TURBT, chemotherapy, radiation, and selection for organ-conservation by response has a 52% overall survival rate. This result is similar to cystectomy-based studies for patients of similar age and clinical stages. The majority of the long-term survivors retain fully functional bladders.

Adult↗

Long-term treatment of osteopetrosis with recombinant human interferon gamma.

BACKGROUND: Congenital osteopetrosis is a rare osteosclerotic bone disease characterized by both a defect in osteoclastic function and reduced generation of superoxide by leukocytes. The disease is frequently fatal during the first decade of life. A six-month trial of therapy with recombinant human interferon gamma-1b in eight patients with osteopetrosis provided evidence of benefit, prompting this study of more prolonged therapy. METHODS: We studied 14 patients with severe osteopetrosis treated with subcutaneous injections of recombinant human interferon gamma-1b (1.5 micrograms per kilogram of body weight per dose) three times per week for at least 6 months; 11 patients were treated for 18 months. We assessed the effect of therapy by evaluating the patients' clinical status, measuring blood counts and biochemical markers of bone turnover, and performing bone marrow imaging and bone biopsies. RESULTS: After 6 months of therapy, all 14 patients had decreases in trabecular-bone area (determined by histomorphometric analysis of bone-biopsy specimens) and increases in bone marrow space (determined by marrow imaging), and the improvement was sustained in the 11 patients treated for 18 months. The mean (+SD) hemoglobin concentration increased from 7.5 +/- 2.9 to 10.5 +/- 0.3 g per deciliter (P = 0.05), and superoxide generation by granulocyte-macrophage colonies increased (P < 0.001) after 18 months of therapy. In six patients for whom pretreatment data were available, there was a 96 percent decrease in the frequency of infections requiring antibiotic therapy during interferon treatment. There were no side effects necessitating the discontinuation of therapy. CONCLUSIONS: Long-term therapy with interferon gamma in patients with osteopetrosis increases bone resorption and hematopoiesis and improves leukocyte function.

Adult↗

Hip dysplasia in spastic cerebral palsy.

Previous reports have noted a relationship between pelvic obliquity and hip dysplasia in spastic cerebral palsy but did not confirm its existence by scientific study. A study is reported that confirms the association of pelvic obliquity with hip dysplasia in spastic cerebral palsy. At presentation of subluxation or dislocation prior to surgery, 80 patients were indexed into five body alignment types. Reclassifications were performed with passage of time in order to study the natural history and effects of surgery. In all cases, hip dysplasia was found to be consistent with the forces related to pelvic obliquity.

Adolescent↗

Selective bladder preservation by combination treatment of invasive bladder cancer.

BACKGROUND: For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. We sought to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured. METHODS: We enrolled 53 consecutive patients with muscle-invading bladder cancer (stages T2 through T4, NXM0) in a trial of transurethral surgery, combination chemotherapy, and irradiation (4000 cGy) with concurrent cisplatin administration. Urologic evaluation of the tumor response directed further therapy: radical cystectomy in the 8 patients who had incomplete responses, additional chemotherapy and radiotherapy (6480 cGy) in the 34 patients who had complete responses or who were unsuited for cystectomy, and alternative care in the 11 patients who could not tolerate either irradiation or chemotherapy. RESULTS: After a median follow-up of 48 months, 24 of the 53 patients (45 percent) were alive and free of detectable tumor. In 31 patients (58 percent) the bladder was free of invasive tumor and functioning well, even though in 9 (17 percent) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 28 patients who had complete responses after initial treatment, 89 percent had functioning tumor-free bladders. CONCLUSIONS: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial that included a group for simultaneous comparison would be required to produce definitive results.

Adult↗

Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Cancer Group.

A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.

Adult↗

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Adult↗

Interval report of a phase I-II study utilizing multiple modalities in the treatment of invasive bladder cancer. A bladder-sparing trial.

Clinicians at the Massachusetts General Hospital have used two cycles of methotrexate, cisplatin, and vinblastine (MCV) before radiotherapy and cisplatin in 53 patients with muscle-invasive bladder cancer. Eleven patients did not complete the protocol, but overall, the toxicity was not formidable. Of the total patients accessioned, 34 are alive. Of the 34 patients in the series who completed the full treatment protocol, the estimated survival rate at 54 months is 77%. This interim analysis suggests that the treatment is achieving at least limited success in saving lives and bladders.

Adult↗

Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.

Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.

Aged↗

Open fractures of the tibia in children.

Forty-one children who had forty-two open fractures of the tibial metaphysis or diaphysis were studied retrospectively. Twelve fractures were Type I; eighteen, Type II; six, Type IIIA; four, Type IIIB; and two, Type IIIC, according to the classification of Gustilo et al. All fractures were irrigated and debrided, and antibiotics were given for a minimum of forty-eight hours after the injury. Twenty fractures were initially treated with external fixation and twenty-two, with immobilization in a plaster cast. Three patients had an early infection of the wound, one of which was associated with osteomyelitis; all were successfully treated. The average time to healing of the fracture was five months (range, two to twenty-one months). The time to union was related to the severity of the soft-tissue injury, the pattern of the fracture, the amount of segmental bone loss, the occurrence of infection, and the use of external fixation. There were six delayed unions. Four patients had an angular malunion of more than 10 degrees, which spontaneously corrected in three. One patient who had a proximal metaphyseal-diaphyseal segmental fracture had a progressive valgus deformity. Four patients who had a severe fracture that was treated with external fixation had more than one centimeter of tibial over-growth. There were no amputations. The incidences of compartment syndrome, vascular injury, infection, and delayed union were similar to those reported for open tibial fractures in adults.

Anterior Compartment Syndrome↗

Long-term experience with flutamide in patients with prostatic carcinoma.

Fifty-two patients with previously untreated metastatic carcinoma of the prostate were treated with flutamide 250 mg tid. Response was classified according to objective and subjective criteria, and duration of response and total survival were chosen as endpoints. Disease manifestations at presentation and tumor burden were studied to determine their relationship, if any, to treatment response and outcome. Total survival was longest in 26 patients who had objective responses (mean 50 months). Patients who failed to respond (n = 13) and those who had subjective responses (n = 13) survived an average of eleven and 17.2 months, respectively. Tumor burden was correlated with response to treatment and total survival; those judged to have a minimum tumor burden had objective responses and survived an average of sixty months. Sixteen other patients who had been previously treated with diethylstilbestrol were also studied. Nine of these had cardiovascular complications while taking diethylstilbestrol, and tolerated flutamide without further complications. Those in remission stayed in remission, and sexual potency returned to 5 patients.

Adenocarcinoma↗